An observational study of quality of motion in the aging cervical spine: sequence of segmental contributions in dynamic fluoroscopy recordings.

BACKGROUND: The term 'physiological motion of the spine' is commonly used although no proper definition exists. Previous work has revealed a consistent sequence of cervical segmental contributions in 80-90% of young healthy individuals. Age has been shown to be associated with a decreased quantity of motion. Therefore, it is of interest to study whether this sequence persists throughout aging. The aim of this prospective cohort study is to investigate if the consistent sequence of cervical segmental contributions in young asymptomatic individuals remains present in elderly asymptomatic individuals. METHODS: In this prospective cohort study, dynamic flexion to extension cinematographic recordings of the cervical spine were made in asymptomatic individuals aged 55-70 years old. Individuals without neck pain and without severe degenerative changes were included. Two recordings were made in each individual with a 2-to-4-week interval (T1 and T2). Segmental rotation of each individual segment between C4 and C7 was calculated to determine the sequence of segmental contributions. Secondary outcomes were segmental range of motion (sRoM) and sagittal alignment. RESULTS: Ten individuals, with an average age of 61 years, were included. The predefined consistent sequence of segmental contributions was found in 10% of the individuals at T1 and 0% at T2. sRoM and total range of motion (tRoM) were low in all participants. There was no statistically significant correlation between sagittal alignment, degeneration and sRoM in the respective segments, nor between cervical lordosis and tRoM. CONCLUSIONS: This study shows that aging is associated with loss of the consistent motion pattern that was observed in young asymptomatic individuals. The altered contribution of the cervical segments during extension did not appear to be correlated to the degree of degeneration or sagittal alignment. Trial registration clinicaltrials.gov NCT04222777, registered 10.01.2020.

EAES and SAGES 2018 consensus conference on acute diverticulitis management: evidence-based recommendations for clinical practice.

BACKGROUND: Acute diverticulitis (AD) presents a unique diagnostic and therapeutic challenge for general surgeons. This collaborative project between EAES and SAGES aimed to summarize recent evidence and draw statements of recommendation to guide our members on comprehensive AD management. METHODS: Systematic reviews of the literature were conducted across six AD topics by an international steering group including experts from both societies. Topics encompassed the epidemiology, diagnosis, management of non-complicated and complicated AD as well as emergency and elective operative AD management. Consensus statements and recommendations were generated, and the quality of the evidence and recommendation strength rated with the GRADE system. Modified Delphi methodology was used to reach consensus among experts prior to surveying the EAES and SAGES membership on the recommendations and likelihood to impact their practice. Results were presented at both EAES and SAGES annual meetings with live re-voting carried out for recommendations with < 70% agreement. RESULTS: A total of 51 consensus statements and 41 recommendations across all six topics were agreed upon by the experts and submitted for members' online voting. Based on 1004 complete surveys and over 300 live votes at the SAGES and EAES Diverticulitis Consensus Conference (DCC), consensus was achieved for 97.6% (40/41) of recommendations with 92% (38/41) agreement on the likelihood that these recommendations would change practice if not already applied. Areas of persistent disagreement included the selective use of imaging to guide AD diagnosis, recommendations against antibiotics in non-complicated AD, and routine colonic evaluation after resolution of non-complicated diverticulitis. CONCLUSION: This joint EAES and SAGES consensus conference updates clinicians on the current evidence and provides a set of recommendations that can guide clinical AD management practice.

Pilot Study: Detection of Gastric Cancer From Exhaled Air Analyzed With an Electronic Nose in Chinese Patients.

The aim of this pilot study is to investigate the ability of an electronic nose (e-nose) to distinguish malignant gastric histology from healthy controls in exhaled breath. In a period of 3 weeks, all preoperative gastric carcinoma (GC) patients (n = 16) in the Beijing Oncology Hospital were asked to participate in the study. The control group (n = 28) consisted of family members screened by endoscopy and healthy volunteers. The e-nose consists of 3 sensors with which volatile organic compounds in the exhaled air react. Real-time analysis takes place within the e-nose, and binary data are exported and interpreted by an artificial neuronal network. This is a self-learning computational system. The inclusion rate of the study was 100%. Baseline characteristics differed significantly only for age: the average age of the patient group was 57 years and that of the healthy control group 37 years ( P value = .000). Weight loss was the only significant different symptom ( P value = .040). A total of 16 patients and 28 controls were included; 13 proved to be true positive and 20 proved to be true negative. The receiver operating characteristic curve showed a sensitivity of 81% and a specificity of 71%, with an accuracy of 75%. These results give a positive predictive value of 62% and a negative predictive value of 87%. This pilot study shows that the e-nose has the capability of diagnosing GC based on exhaled air, with promising predictive values for a screening purpose.

In toto resection of a rare intradural extramedullary cavernous malformation on the S1 nerve root: illustrative case.

BACKGROUND: Cavernous malformations (CMs) are vascular malformations that usually occur in the brain and occasionally in the spine. Most CMs are sporadic, but they can also be caused by heterozygous cerebral cavernous malformation (CCM) gene mutations. This case describes an intradural extramedullary CM in a unique location, within a fascicle of the S1 nerve root. This tumor was found to have a CCM2 mutation. An operative video demonstrates the surgical procedure used to remove this S1 intradural extramedullary CM. OBSERVATIONS: A 61-year-old male with an intradural extramedullary CM, located within a fascicle of the S1 nerve root, presented with pain and neurological symptoms. Additional imaging revealed two CCMs. The S1 CM was removed in toto. Subsequently, genetic screening revealed a CCM2 mutation. LESSONS: Given the rarity of a radicular CM, diagnosis can be challenging. CMs should be considered in patients with radicular pain and corresponding nerve root thickening. When a CM is suspected, imaging of the complete neuraxis should be performed. If multiple CMs are found, genetic screening is indicated. Complete resection of the CM yields good clinical results. The operative video in this case might help surgeons encountering this rare pathology to prepare for surgery. https://thejns.org/doi/10.3171/CASE24270.

A randomized controlled trial with extended long-term follow-up: Quality of cervical spine motion after anterior cervical discectomy (ACD) or anterior cervical discectomy with arthroplasty (ACDA).

Introduction: In previous research, a consistent sequence of segmental contributions during dynamic extension X-rays of the cervical spine was observed in 80-90% of healthy participants. Research question: To investigate whether this previously defined 'normal' sequence of segmental contributions was present in patients who underwent anterior cervical discectomy with arthroplasty (ACDA) or anterior cervical discectomy (ACD). Materials & methods: A randomized controlled trial with extended follow-up was conducted. Patients with single level cervical degenerative radiculopathy with a surgical indication were included and randomized. Dynamic X-ray recordings were made before surgery, one-year post-operative, and at long term follow-up. Results: A total of 27 patients were included, three in an ACDA pilot group and 24 were randomized to receive ACDA (N = 12) or ACD (N = 12). A total of 20 patients were available for follow-up. Preoperatively, 16.7% of patients in the ACDA group and 58.3% of patients in the ACD group showed a normal sequence. One-year post-operative, 66.7% showed a normal sequence in the ACDA group versus 30.0% in the ACD group (p = 0.036). After an average of 11-years follow-up, a normal sequence was observed in 9.1% of patients in the ACDA group and in none of the patients in the ACD group (p = 0.588). Discussion & conclusion: These findings suggest that while ACDA can restore and preserve a normal sequence of segmental contributions in the short term, this effect is not maintained in the long term. Throughout the process of ageing, not only the quantity, but also the quality of motion changes.

Mother and daughter with a SMARCE1 mutation resulting in a cervical clear cell meningioma at an identical location: illustrative cases.

BACKGROUND: A rare meningioma subtype is a clear cell (CC) meningioma, which can be associated with a SMARCE1 gene mutation. Manifestation of a CC meningioma in the cervical spine is unusual. In the current case, both mother and daughter present with a CC meningioma at an identical cervical location. OBSERVATIONS: A 67-year-old patient with an intradural extramedullary mass at the level of C5 presented with progressive myelopathy. The mass was resected through a ventral approach by a two-level corpectomy with an expandable cage and instrumentation. The daughter of this patient appeared to have had an intradural extramedullary mass at C5 at the age of 20, which was resected through a posterior approach. Pathological investigation of both tumors revealed CC meningioma. Genetic testing of the daughter revealed a SMARCE1 mutation. LESSONS: It is of major importance to consider a SMARCE1 mutation in elderly presenting with a CC meningioma, which is still uncommon in current practice. This could lead to timely diagnostics in the succeeding generation. Complete resection of a CC meningioma is important because of the high recurrence rate. Routine follow-up should therefore be performed in the postoperative period. An anterior approach should be considered for a ventral cervical CC meningioma.

Predicting Survival in Patients Presenting With Spinal Epidural Metastases: The Limburg Spinal Metastasis Score.

BACKGROUND: Patients with spinal epidural metastases (SEM) often experience a reduction in ambulatory status and, thus, the quality of life. Predicting which patients will benefit from a surgical intervention remains a challenge. Life expectancy is an essential factor to be considered in surgical decision-making, although not the only one. Prediction models can add value in surgical decision-making. The goal of this study was to develop and internally validate a novel model (Limburg spinal metastases score [LSMS]) and compare the predictive value with 2 commonly used models: modified Bauer score and Oswestry Spinal Risk Index (OSRI). METHODS: We retrospectively analyzed 144 consecutive patients who underwent surgical decompression for SEM in our centers between November 2006 and December 2020. Clinical and surgical parameters were evaluated. The novel prediction model was based on multivariate analysis and was internally validated. External validation of the 2 most commonly used prediction models was performed. RESULTS: The median survival was 17 months, 55.7% of the immobile patients regained ambulation postoperatively. In 50 patients (34.7%), at least 1 complication occurred within 30 days after surgery. The LSMS consists of 4 parameters: primary tumor type, Karnofsky performance score, presence of visceral metastases, and presence of multiple spinal metastases. Bootstrap internal validation of the model developed on this cohort yielded an optimism-corrected c-statistic of 0.75 (95% CI: 0.71-0.80). The c-statistic of the OSRI score and the Bauer score was 0.69 (95% CI: 0.64-0.74) and 0.67 (95% CI: 0.62-0.72), respectively. CONCLUSION: The LSMS consists of 4 parameters to assist surgical decision-making for patients with SEM. The score is easy to use and appears more accurate in our population in comparison with previous existing models. CLINICAL RELEVANCE: A novel prediction model was developed to aid in surgical decision-making for patients with spinal epidural metastases.

Methodology of economic evaluations in spine surgery: a systematic review and qualitative assessment.

OBJECTIVES: The present study is a systematic review conducted as part of a methodological approach to develop evidence-based recommendations for economic evaluations in spine surgery. The aim of this systematic review is to evaluate the methodology and quality of currently available clinical cost-effectiveness studies in spine surgery. STUDY DESIGN: Systematic literature review. DATA SOURCES: PubMed, Web of Science, Embase, Cochrane, Cumulative Index to Nursing and Allied Health Literature, EconLit and The National Institute for Health Research Economic Evaluation Database were searched through 8 December 2022. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Studies were included if they met all of the following eligibility criteria: (1) spine surgery, (2) the study cost-effectiveness and (3) clinical study. Model-based studies were excluded. DATA EXTRACTION AND SYNTHESIS: The following data items were extracted and evaluated: pathology, number of participants, intervention(s), year, country, study design, time horizon, comparator(s), utility measurement, effectivity measurement, costs measured, perspective, main result and study quality. RESULTS: 130 economic evaluations were included. Seventy-four of these studies were retrospective studies. The majority of the studies had a time horizon shorter than 2 years. Utility measures varied between the EuroQol 5 dimensions and variations of the Short-Form Health Survey. Effect measures varied widely between Visual Analogue Scale for pain, Neck Disability Index, Oswestry Disability Index, reoperation rates and adverse events. All studies included direct costs from a healthcare perspective. Indirect costs were included in 47 studies. Total Consensus Health Economic Criteria scores ranged from 2 to 18, with a mean score of 12.0 over all 130 studies. CONCLUSIONS: The comparability of economic evaluations in spine surgery is extremely low due to different study designs, follow-up duration and outcome measurements such as utility, effectiveness and costs. This illustrates the need for uniformity in conducting and reporting economic evaluations in spine surgery.

Advocating uniformity in spine surgery: a practical disease-specific guideline for trial-based economic evaluations.

OBJECTIVES: Despite the availability of general and national guidelines for the conduct and reporting of economic evaluations, there is heterogeneity in economic evolutions concerning spine surgery. This is partly the result of differing levels of adherence to the existing guidelines and the lack of disease-specific recommendations for economic evaluations. The extensive heterogeneity in study design, follow-up duration and outcome measurements limit the comparability of economic evaluations in spine surgery. This study has three objectives: (1) to create disease-specific recommendations for the design and conduct of trial-based economic evaluations in spine surgery, (2) to define recommendations for reporting economic evaluations in spine surgery as a complement to the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) 2022 checklist and (3) to discuss methodological challenges and defining the need for future research. DESIGN: A modified Delphi method according to the RAND/UCLA Appropriateness Method. SETTING: A four-step process was followed to create and validate disease-specific statements and recommendations for the conduct and reporting of trial-based economic evaluations in spine surgery. Consensus was defined as >75% agreement. PARTICIPANTS: A total of 20 experts were included in the expert group. Validation of the final recommendations was obtained in a Delphi panel, which consisted of 40 researchers in the field who were not included in the expert group. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary outcome measure is a set of recommendations for the conduct and reporting, as a complement to the CHEERS 2022 checklist, of economic evaluations in spine surgery. RESULTS: A total of 31 recommendations are made. The Delphi panel confirmed consensus on all of the recommendations in the proposed guideline. CONCLUSION: This study provides an accessible and practical guideline for the conduct of trial-based economic evaluations in spine surgery. This disease-specific guideline is a complement to existing guidelines, and should aid in reaching uniformity and comparability.

Clinical adjacent segment pathology after anterior cervical discectomy, with and without fusion, for cervical degenerative disc disease: A single center retrospective cohort study with long-term follow-up.

Introduction: Clinical adjacent segment pathology (CASP) continues to be a cause of concern after anterior surgical treatment for single- or multilevel cervical degenerative disc disease (CDDD). The current literature reports inconsistent incidence rates and contended risk factors in the development of CASP. Research question: The aim is to determine the incidence of additional CASP-related surgeries after anterior cervical discectomy with fusion (ACDF) or without fusion (ACD) for CDDD. Secondary outcomes include risk factors for the development of CASP and long-term clinical outcomes. Materials & methods: This is a single-center, retrospective cohort study with a long-term follow up. Patients undergoing ACD(F) for CDDD between January 2012 and December 2019 were included. Results: A total of 601 patients were included, with an average follow-up period of 5.0 years. Most patients underwent ACDF with stand-alone cages (87.7%). CASP developed in 58 (9.7%) patients, 41 (70.7%) of which required additional adjacent level surgery. ACD significantly accelerated the development of CASP. The C2-C7 Cobb angle appeared less lordotic upon early post-operative imaging in ACDF patients that later-on developed CASP. Baseline degeneration at the index level and adjacent levels was not significantly different between patients with and without CASP. Discussion & conclusion: In this retrospective cohort, we observe a relatively low rate of additional surgery for CASP in ACDF with stand-alone cages. We suggest that surgical technique, fusion, segmental kyphosis and natural degeneration play a multifactorial role in the development of CASP. Complication rates were low and clinical outcomes were similar for all techniques used.

A Systematic Review on Neurological Outcomes for Cervical Degenerative Myelopathy After Anterior Decompression Surgery: Motion Preservation vs Fusion.

BACKGROUND: Although it is well established that surgically treated patients with cervical degenerative myelopathy (CDM) improve irrespective of the anterior decompression technique used, no consensus exists on what technique is superior in terms of neurological recovery. A general concern exists that anterior cervical discectomy with arthroplasty (ACDA) leads to less favorable outcomes in CDM due to microtrauma caused by preserved mobility. It is remarkable that current literature mainly uses pain scores to assess clinical outcomes after anterior decompression surgery, especially considering that pain may not be the most relevant outcome for CDM. This systematic review evaluated the literature concerning neurological outcomes in patients with CDM treated with anterior decompression surgery and assessed by validated myelopathy scores. METHODS: Systematic searches were carried out in PubMed, EMBASE, Web of Science, CINAHL, and the Cochrane Library. Prospective studies were included when patients with isolated CDM were treated with anterior decompression surgery, and a validated myelopathy outcome score was used. RESULTS: A total of 11 studies were included from the 16,032 identified studies. All studies used the modified Japanese Orthopedic Association (JOA) outcome score and showed improvement for all anterior techniques. The mean improvement in anterior cervical discectomy and fusion (ACDF) was 4.80 and 3.64 for the modified JOA and JOA outcome scores, respectively. The JOA for ACDA showed a mean improvement of 5.51. The overall quality of the included articles was low to moderate according to the Cochrane tool. CONCLUSION: Neurological recovery of CDM is similar after all anterior decompression techniques, including ACDA when compared with ACDF. CLINICAL RELEVANCE: The current literature gives no reason to dissuade the use of ACDA in cervical myelopathy.

Double-center observational study of minimally invasive sacroiliac joint fusion for sacroiliac joint dysfunction: one-year results.

BACKGROUND: For a substantial part of patients with chronic low back pain, the origin is located in the sacroiliac joint (SIJ). Minimally invasive sacroiliac joint fusion (MISJF) is increasingly being implemented as a treatment option in SIJ dysfunction. Despite remaining controversy, evidence continues to increase. This study evaluates the clinical results and safety of MISJF in a double-center consecutive case series in patients with SIJ dysfunction over a one-year observation period. METHODS: SIJ complaints were diagnosed after history taking, physical examination and least a 50% reduction of SIJ pain 30-60 min following image-guided injection. Primary outcome measures were patient reported outcome measurements (PROMs), consisting of Visual Analogue Scale (VAS) pain score and EuroQol 5-dimensions 3-levels (EQ-5D-3L). Patients' perspectives on the effects of surgery were collected through questionnaires. Secondary outcome measures were implant positioning and (serious) adverse events ((S)AE's). RESULTS: A total of 29 patients were included. In 44.8% of patients, SIJ dysfunction was of postpartum origin. The mean VAS-pain score improved from 7.83 (± 1.71) to 4.97 (± 2.63) postoperatively (p < 0.001). EQ-5D-3L score improved from 0.266 (± 0.129) to 0.499 (± 0.260) postoperatively (p < 0.001). Opioid consumption decreased from 44.8 to 24.1% postoperatively (p = 0.026). In 13.7% of patients, an (S)AE occurred. CONCLUSION: MISJF appears to be an effective and safe procedure in this cohort. Statistically significant and clinically relevant improvements in pain and quality of life were observed one-year postoperatively. Future studies should focus on the long-term outcomes to further evaluate the safety and effectiveness of MISJF.

Research protocol: Cervical Arthroplasty Cost Effectiveness Study (CACES): economic evaluation of anterior cervical discectomy with arthroplasty (ACDA) versus anterior cervical discectomy with fusion (ACDF) in the surgical treatment of cervical degenerative disc disease - a randomized controlled trial.

INTRODUCTION: To date, there is no consensus on which anterior surgical technique is more cost-effective in treating cervical degenerative disc disease (CDDD). The most commonly used surgical treatment for patients with single- or multi-level symptomatic CDDD is anterior cervical discectomy with fusion (ACDF). However, new complaints of radiculopathy and/or myelopathy commonly develop at adjacent levels, also known as clinical adjacent segment pathology (CASP). The extent to which kinematics, surgery-induced fusion, natural history, and progression of disease play a role in the development of CASP remains unclear. Anterior cervical discectomy with arthroplasty (ACDA) is another treatment option that is thought to reduce the incidence of CASP by preserving motion in the operated segment. While ACDA is often discouraged, as the implant costs are higher while the clinical outcomes are similar to ACDF, preventing CASP might be a reason for ACDA to be a more cost-effective technique in the long term. METHODS AND ANALYSIS: In this randomized controlled trial, patients will be randomized to receive ACDF or ACDA in a 1:1 ratio. Adult patients with single- or multi-level CDDD and symptoms of radiculopathy and/or myelopathy will be included. The primary outcome is cost-effectiveness and cost-utility of both techniques from a healthcare and societal perspective. Secondary objectives are the differences in clinical and radiological outcomes between the two techniques, as well as the qualitative process surrounding anterior decompression surgery. All outcomes will be measured at baseline and every 6 months until 4 years post-surgery. DISCUSSION: High-quality evidence regarding the cost-effectiveness of both ACDA and ACDF is lacking; to date, there are no prospective trials from a societal perspective. Considering the aging of the population and the rising healthcare costs, there is an urgent need for a solid clinical cost-effectiveness trial addressing this question. TRIAL REGISTRATION: ClinicalTrials.gov NCT04623593. Registered on 29 September 2020.

Ossification of the posterior longitudinal ligament at the craniocervical junction presenting with Brown-Séquard syndrome: A case report.

BACKGROUND: Several case reports about spinal cord compression due to hyperostosis at the craniocervical junction are available. However, compression at C1-C2 solely due to ossification of the posterior longitudinal ligament (OPLL) is rare. CASE DESCRIPTION: A 50-year-old Asian male, with a history of lumbar spinal canal stenosis, presented with a progressive quadriparesis within 3 months. Imaging showed central OPLL at the C1-C2 level contributing to severe spinal cord compression. The patient improved neurologically after a C1-C2 laminectomy. CONCLUSION: A patient presented with a progressive Brown-Séquard syndrome due to OPLL at the craniocervical junction (C1-C2 level) and improved following a decompressive laminectomy.

Neurosarcoidosis with hydrocephalus as a first presenting sign: a unique case report.

There is a possible relationship with cerebral ischemic events and neurosarcoidosis. It should be considered in the differential diagnosis in a case of unexplained hydrocephalus, vascular white matter lesions and vasculitis related findings.

Evidence-based recommendations for economic evaluations in spine surgery: study protocol for a Delphi consensus.

INTRODUCTION: Considering the rising global healthcare expenses, economic evaluations are more important than ever. Even though the number of studies regarding costs and cost-effectiveness is increasing, the quality of these studies remains relatively low. This is mainly caused by abundant heterogeneity in methods used for determining, calculating and reporting cost data, despite current general guidelines for the conduct of economic evaluations. Disease-specific recommendations for the conduct of economic evaluations in the field of spine surgery, as complement to existing general guidelines, will ameliorate overall research quality, comparability and interpretability and thus, the overall quality. We aim to provide expert-based recommendations for the design, conduct, and reporting of economic evaluations in spine surgery. METHODS AND ANALYSIS: A modified Delphi study will be conducted to formulate expert-based recommendations. The following steps will be taken:(1) The conduct of a systematic review to identify relevant publications and identify relevant authors. Formation of an expert group and a Delphi-panel. (2) Drafting of statements based on articles included in the systematic literature review. Validation of drafted statements by the expert group. Step 2 can be repeated up to three times, statements can be discarded and adjusted in these rounds. Statements with more than 75% agreement will be accepted as consensus statements. (3) Validation of statements by the Delphi-panel. (4) Final recommendations. ETHICS AND DISSEMINATION: The underlying work is based on existing literature and published data and does not include participation of patients, and thus does not require ethical review approval. The final recommendations are intended for (clinical) researchers in the field of cost-effectiveness in spine surgery. The Delphi method ensures that the final output reflects the opinions of international participants and gives insight in the adherence level to the recommendations. The aim is to reach uniformity in design, conduct and reporting of these studies, as is currently lacking. This will provide a solid basis to determine cost-effectiveness of spine surgeries and consequently aid to limit the rising healthcare costs. The findings of this study and the final recommendations will be disseminated in conferences and seminars and will be published in an international peer-reviewed journal.

Tumor microenvironment-derived S100A8/A9 is a novel prognostic biomarker for advanced melanoma patients and during immunotherapy with anti-PD-1 antibodies.

BACKGROUND: Predicting metastasis in melanoma patients is important for disease management and could help to identify those who might benefit from adjuvant treatment. The aim of this study was to investigate whether the tumor microenvironment-derived protein S100A8/A9 qualifies as prognostic marker for melanoma patients, also in the setting of immunotherapy. METHODS: S100A8/A9 gene and protein expression were analyzed on melanocytic nevi, primary melanomas and metastases using a cDNA library and three independent tissue-microarrays (TMA). Serum levels of S100A8/A9 were measured using a specific ELISA in two independent cohorts of 354 stage III and stage IV melanoma patients as well as in two independent cohorts of patients treated with the PD-1 antibody pembrolizumab. RESULTS: cDNA analysis revealed an upregulation of S100A8 and S100A9 gene expression in melanoma metastases compared to primary melanomas. Significantly higher numbers of infiltrating S100A8/A9 positive cells were found in tissue samples of metastasizing primary melanomas compared to non-metastasizing melanomas (P < .0001) and in melanomas of short-term survivors compared to long-term survivors (P < .0001). Serum S100A8/A9 levels > 5.5 mg/l were associated with impaired overall survival in two independent cohorts (both P < .0001). Importantly, patients with serum elevated S100A8/A9 treated with pembrolizumab showed significantly impaired survival compared to patients with lower S100A8/A9 levels (cohort 1: P = .0051; cohort 2: P < .0001). CONCLUSIONS: The tumor microenvironment-associated protein S100A8/A9 serves as a novel prognostic marker for metastasis and survival of metastatic melanoma patients and predicts response to immunotherapy with pembrolizumab. These data underscore the significance of tumor microenvironment-derived factors as suitable biomarkers for melanoma.

Clinical Outcomes After Unilateral Adrenalectomy for Primary Aldosteronism.

Importance: In addition to biochemical cure, clinical benefits after surgery for primary aldosteronism depend on the magnitude of decrease in blood pressure (BP) and use of antihypertensive medications with a subsequent decreased risk of cardiovascular and/or cerebrovascular morbidity and drug-induced adverse effects. Objective: To evaluate the change in BP and use of antihypertensive medications within an international cohort of patients who recently underwent surgery for primary aldosteronism. Design, Setting, and Participants: A cohort study was conducted across 16 referral medical centers in Europe, the United States, Canada, and Australia. Patients who underwent unilateral adrenalectomy for primary aldosteronism between January 2010 and December 2016 were included. Data analysis was performed from August 2017 to June 2018. Unilateral disease was confirmed using computed tomography, magnetic resonance imaging, and/or adrenal venous sampling. Patients with missing or incomplete preoperative or follow-up data regarding BP or corresponding number of antihypertensive medications were excluded. Main Outcomes and Measures: Clinical success was defined based on postoperative BP and number of antihypertensive medications. Cure was defined as normotension without antihypertensive medications, and clear improvement as normotension with lower or equal use of antihypertensive medications. In patients with preoperative normotensivity, improvement was defined as postoperative normotension with lower antihypertensive use. All other patients were stratified as no clear success because the benefits of surgery were less obvious, mainly owing to postoperative, persistent hypertension. Clinical outcomes were assessed at follow-up closest to 6 months after surgery. Results: On the basis of inclusion and exclusion criteria, a total of 435 patients (84.6%) from a cohort of 514 patients who underwent unilateral adrenalectomy were eligible. Of these patients, 186 (42.3%) were women; mean (SD) age at the time of surgery was 50.7 (11.4) years. Cure was achieved in 118 patients (27.1%), clear improvement in 135 (31.0%), and no clear success in 182 (41.8%). In the subgroup classified as no clear success, 166 patients (91.2%) had postoperative hypertension. However, within this subgroup, the mean (SD) systolic and diastolic BP decreased significantly by 9 (22) mm Hg (P < .001) and 3 (15) mm Hg (P = .04), respectively. Also, the number of antihypertensive medications used decreased from 3 (range, 0-7) to 2 (range, 0-6) (P < .001). Moreover, in 75 of 182 patients (41.2%) within this subgroup, the decrease in systolic BP was 10 mm Hg or greater. Conclusions and Relevance: In this study, for most patients, adrenalectomy was associated with a postoperative normotensive state and reduction of antihypertensive medications. Furthermore, a significant proportion of patients with postoperative, persistent hypertension may benefit from adrenalectomy given the observed clinically relevant and significant reduction of BP and antihypertensive medications.