International Consensus Group Research Articles

Classification of schwannomas and the new naming convention for "neurofibromatosis-2": Genetic updates and international consensus recommendation.

Despite their similar nomenclature, Neurofibromatosis type 1 (NF1) and "Neurofibromatosis type 2" are discrete and clinically distinguishable entities. The name of "neurofibromatosis type 2" has been changed to NF2-related schwannomatosis, to reflect the fact that neurofibromas do not occur in this syndrome and therefore the name "Neurofibromatosis" is factually incorrect. Furthermore, multiple schwannomas, a hallmark feature of NF2, can also occur in patients with mutations in genes including SMARCB1 and LZTR1, all exhibiting overlapping clinical features. Current understanding suggests that schwannomatosis (SWN) encompasses a range of clinical presentations consisting of clearly defined, separate subtypes which share a common phenotype of schwannomas. Recognizing these newly emerging subtypes, the International Consensus Group on Neurofibromatosis Diagnostic Criteria (I-NF-DC) proposed a revised nomenclature for NF2 and related disorders in 2022. This review article focuses on this critical update in diagnostic terminology, highlighting the key gene-related SWN subtypes relevant to neuroradiologists. By emphasizing molecular testing alongside clinical features, the revised system facilitates a more precise diagnosis, potentially paving the way for personalized treatment strategies. Additionally, the flexible structure accommodates future discoveries of genes associated with SWN.

An International Consensus Practical Guide on Left Atrial Appendage Closure for the Non-implanting Physician: Executive Summary.

Many patients with atrial fibrillation (AF) who are in need of stroke prevention are not treated with oral anticoagulation or discontinue treatment shortly after its initiation. Despite the availability of direct oral anticoagulants (DOACs), such undertreatment has improved somewhat but is still evident. This is due to continued risks of bleeding events or ischemic strokes while on DOAC, poor treatment compliance, or aversion to anticoagulant therapy. Because of significant improvements in procedural safety over the years left atrial appendage closure (LAAC), using a catheter-based, device implantation approach, is increasingly favored for the prevention of thromboembolic events in AF patients who cannot have long-term oral anticoagulation. This article is an executive summary of a practical guide recently published by an international expert consensus group, which introduces the LAAC devices and briefly explains the implantation technique. The indications and device follow-up are more comprehensively described. This practical guide, aligned with published guideline/guidance, is aimed at those non-implanting physicians who may need to refer patients for consideration of LAAC.

205. MINIMALLY INVASIVE IVOR LEWIS ESOPHAGECTOMY WITH TOTAL MEDIASTINAL LYMPHADENECTOMY FOR THORACIC ESOPHAGEAL CANCER: SHORT- AND LONG-TERM OUTCOMES IN 139 PATIENTS

Abstract Background The McKeown approach is a standard surgery for thoracic esophageal cancer in Japan, as lymph node dissection of upper mediastinum and neck is mandatory. The thoracoscopic approach allows access to the lymph node chain along the laryngeal nerves from the chest and led us to introduce minimally invasive Ivor Lewis esophagectomy (MIILE) with radical lymphadenectomy for middle and lower esophageal cancer. Although circular-stapled anastomosis is popular in MIILE, the frequency of anastomotic complications has been reported to be high. We introduced MIILE with linear-stapled anastomosis in 2010. Methods To evaluate the short- and long-term outcomes of MIILE with radial lymphadenectomy and linear stapled anastomosis, we performed a retrospective cohort study of 139 consecutive patients. The endpoints included overall complications, anastomotic leak rate, nutritional status at 12 months after MIILE, and 5-year overall survival, and disease-free survival. Surgical Procedure After laparoscopic gastric tube construction, thoracoscopic or robotic esophagectomy with total mediastinal lymphadenectomy was done in the prone position. ICG angiography was used to assess gastric tube viability and sacrifice the ischemic portion in recent cases. Esophago-gastric anastomosis was performed using a linear stapler. The opening was closed with interrupted sutures and covered with the omentum to secure the anastomosis. Results There was 122 male and 17 female patients with median age of 69 years. Preoperative diagnosis was stage I/II/III/IV in 44/46/37/12 patients. Pathology results were SCC in 108 cases. Tumor location was middle/lower/EGJ in 58/64/17 patients. Preoperative chemotherapy or CRT was administered in 77 patients. Median thoracic surgery time was 297 minutes and blood loss was 53 mL. Median hospital stay was 17 days. The short-term complication rate of grade IIIa or higher was 8.7%. Anastomotic leak occurred in 8 patients (5.8%), three of whom required intervention. No leakage occurred after introduction of intraoperative ICG angiography. 90-day mortality was 0.7%. With a median follow-up of 41 months, 5-year overall survival rate was 68.3% and disease-free survival rates was 56.7%. For the 65 SCC patients with clinical stage II/III disease, 5-year OS rate was 58.7%. During follow-up period, 2 patients (1.4%) required balloon dilatation due to anastomotic stenosis. At 12 months after MIILE, the mean weight loss was 11.6% and the mean albumin level was 3.9. Discussion Compared to benchmark complication rates reported by the international Esophagectomy Complication Consensus Group (ECCG), the overall complication rate (47% vs. 59%) was not significantly lower, but the anastomotic leak rate was significantly lower (5.8 vs. 11.4%). Overall survival, disease-free survival, and nutritional outcomes were similar to those reported in Japanese clinical trials. Conclusions MIILE with linear-stapled anastomosis is a safe procedure with a low rate of serious complications. Survival and nutritional outcomes were excellent. It may be recommended as a standard procedure for lower and middle esophageal cancer. https://www.dropbox.com/scl/fi/z6zyllnmie9qh3zhz2wd5/Okabe_ISDE.wmv?rlkey=4mig28fv5z2vhaui31tbk0mr9&dl=0

Anti-B-Cell-Activating Factor (BAFF) Therapy: A Novel Addition to Autoimmune Disease Management and Potential for Immunomodulatory Therapy in Warm Autoimmune Hemolytic Anemia.

Although rituximab is not specifically approved for the treatment of warm autoimmune hemolytic anemia (WAIHA), the First International Consensus Group recommends considering its use as part of the initial therapy for patients with severe disease and as a second-line therapy for primary WAIHA. Some patients do not respond to rituximab, and relapses are common. These relapses are associated with elevated B-cell-activating factor (BAFF) levels and the presence of quiescent long-lived plasma cells (LLPCs) in the spleen. A new group of immunomodulatory drugs, B-cell-activating factor inhibitors (BAFF-i), demonstrated efficacy in multiple autoimmune diseases and have the potential to improve WAIHA treatment outcomes by targeting B-cells and LLPCs. This article reviews the role of BAFF in autoimmune disorders and the currently available literature on the use of BAFF-directed therapies in various immunologic disorders, including WAIHA. Collectively, the clinical data thus far shows robust potential for targeting BAFF in WAIHA therapy.

Glucose Targets Using Continuous Glucose Monitoring Metrics in Older Adults With Diabetes: Are We There Yet?

The older population is increasing worldwide and up to 30% of older adults have diabetes. Older adults with diabetes are at risk of glucose-related acute and chronic complications. Recently, mostly in type 1 diabetes (T1D), continuous glucose monitoring (CGM) devices have proven beneficial in improving time in range (TIR glucose, 70-180 mg/dL or glucose 3.9-10 mmol/L), glycated hemoglobin (HbA1c), and in lowering hypoglycemia (time below range [TBR] glucose <70 mg/dL or glucose <3.9 mmol/L). The international consensus group formulated CGM glycemic targets relating to older adults with diabetes based on very limited data. Their recommendations, based on expert opinion, were aimed at mitigating hypoglycemia in all older adults. However, older adults with diabetes are a heterogeneous group, ranging from healthy to very complex frail individuals based on chronological, biological, and functional aging. Recent clinical trial and real-world data, mostly from healthy older adults with T1D, demonstrated that older adults often achieve CGM targets, including TIR recommended for non-vulnerable groups, but less often meet the recommended TBR <1%. Existing data also support that hypoglycemia avoidance may be more strongly related to minimization of glucose variability (coefficient of variation [CV]) rather than lower TIR. Very limited data are available for glucose goals in older adults adjusted for the complexity of their health status. Herein, we review the bidirectional associations between glucose and health status in older adults with diabetes; use of diabetes technologies, and their impact on glucose control; discuss current guidelines; and propose a new set of CGM targets for older adults with insulin-treated diabetes that are individualized for health and living status.

Headache in the adult population of Cameroon: prevalence estimates and demographic associations from a cross-sectional nationwide population-based study

BackgroundKnowledge of headache prevalence, and the burdens attributable to headache disorders, remains incomplete in sub-Saharan Africa (SSA): reliable studies have been conducted only in Zambia (southern SSA) and Ethiopia (eastern SSA). As part of the Global Campaign against Headache, we investigated the prevalence of headache in Cameroon, in Central SSA.MethodsWe used the same methodology as the studies in Zambia and Ethiopia, employing cluster-randomized sampling in four regions of Cameroon, selected to reflect the country’s geographic, ethnic and cultural diversities. We visited, unannounced, randomly selected households in each region, and randomly selected one adult member (aged 18–65 years) of each. Trained interviewers administered the Headache-Attributed Restriction, Disability and Impaired Participation (HARDSHIP) structured questionnaire, developed by an international expert consensus group and translated into Central African French. Demographic enquiry was followed by diagnostic questions based on ICHD-3 criteria.ResultsHeadache was a near-universal experience in Cameroon (lifetime prevalence: 94.8%). Observed 1-year prevalence of headache was 77.1%. Age- and gender-adjusted estimates were 76.4% (95% confidence interval: 74.9–77.9) for any headache, 17.9% (16.6–19.3) for migraine (definite + probable), 44.4% (42.6–46.2) for tension-type headache (TTH; also definite + probable), 6.5% (5.7–7.4) for probable medication-overuse headache (pMOH) and 6.6% (5.8–7.6) for other headache on ≥ 15 days/month (H15 +). One-day prevalence (“headache yesterday”) was 15.3%. Gender differentials were as expected (more migraine and pMOH among females, and rather more TTH among males). pMOH increased in prevalence until age 55 years, then declined somewhat. Migraine and TTH were both associated with urban dwelling, pMOH, in contrast, with rural dwelling.ConclusionsHeadache disorders are prevalent in Cameroon. As in Zambia and Ethiopia, estimates for both migraine and TTH exceed global mean estimates. Attributable burden is yet to be reported, but these findings must lead to further research, and measures to develop and implement headache services in Cameroon, with appropriate management and preventative strategies.

"Window of Opportunity" in Ocular Graft-Versus-Host Disease Treatment: Results of a Longitudinal Study and Case Reports.

To perform a longitudinal study for determining the development of ocular graft-versus-host disease (oGVHD) after allogeneic hematopoietic stem cell transplant (HSCT) and report cases that illustrate the "window of opportunity" concept in oGVHD treatment. Patients (n=61) were examined at prescheduled clinic visits before HSCT and three-month intervals after HSCT for 2 years. The presence or absence of oGVHD was determined using the international chronic oGVHD consensus group diagnostic criteria. Ocular surface washings (OSW) were obtained at each visit and analyzed for cytokine levels. In the longitudinal study, 26.2% (n=16; progressed group) developed either probable (11.5%, n=7) or definite oGVHD (14.8%, n=9). In the progressed group, clinically significant changes in signs (corneal staining and Schirmer I test) and symptoms at the post-HSCT visit as compared with the pre-HSCT visit occurred at 9 months. Significant differences in clinical signs and symptoms (whether average post-HSCT values or changes in values over pre-HSCT levels) between the progressed and nonprogressed groups occurred at a 9-month visit or later. In the progressed group, 55.6% of eyes that had negative matrix metalloproteinase 9 (MMP-9) test at pre-HSCT turned MMP-9 positive at 3 to 6 months post-HSCT. In the progressed group, interleukin 8 levels in OSW were significantly increased at 6 months post-HSCT. In the case reports, the "window of opportunity" was detected by MMP-9 turning positive, early corneal staining, interleukin 8 increase in OSW, and peripheral corneal epithelial thinning, which resolved with treatment initiation. A "window of opportunity" exists before patients developing symptomatic tear-deficient dry eye after HSCT for initiating treatment that may preempt oGVHD development; however, larger-scale longitudinal studies are needed for definitive recommendations.

PRECISE Version 2: Updated Recommendations for Reporting Prostate Magnetic Resonance Imaging in Patients on Active Surveillance for Prostate Cancer

Background and objectiveThe Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) recommendations standardise the reporting of prostate magnetic resonance imaging (MRI) in patients on active surveillance (AS) for prostate cancer. An international consensus group recently updated these recommendations and identified the areas of uncertainty. MethodsA panel of 38 experts used the formal RAND/UCLA Appropriateness Method consensus methodology. Panellists scored 193 statements using a 1–9 agreement scale, where 9 means full agreement. A summary of agreement, uncertainty, or disagreement (derived from the group median score) and consensus (determined using the Interpercentile Range Adjusted for Symmetry method) was calculated for each statement and presented for discussion before individual rescoring. Key findings and limitationsParticipants agreed that MRI scans must meet a minimum image quality standard (median 9) or be given a score of ‘X’ for insufficient quality. The current scan should be compared with both baseline and previous scans (median 9), with the PRECISE score being the maximum from any lesion (median 8). PRECISE 3 (stable MRI) was subdivided into 3-V (visible) and 3-NonV (nonvisible) disease (median 9). Prostate Imaging Reporting and Data System/Likert ≥3 lesions should be measured on T2-weighted imaging, using other sequences to aid in the identification (median 8), and whenever possible, reported pictorially (diagrams, screenshots, or contours; median 9). There was no consensus on how to measure tumour size. More research is needed to determine a significant size increase (median 9). PRECISE 5 was clarified as progression to stage ≥T3a (median 9). Conclusions and clinical implicationsThe updated PRECISE recommendations reflect expert consensus opinion on minimal standards and reporting criteria for prostate MRI in AS.

Prevalence, incidence and risk factors for rugby-related injuries: A survey of the Safari Sevens tournament.

Rugby-related injuries are a leading cause of dropout from competitive sports, high insurance compensation, disability and socioeconomic marginalisation. The debilitating effect of these injuries on players may deny them the benefits associated with rugby and can lead to premature termination of a rugby career. To determine the prevalence, incidence and risk factors for rugby-related injuries among male Safari Sevens rugby tournament players in Kenya. Following ethical approval and clearance, this cross-sectional study was carried out among October 2021 teams of male players in the Safari Sevens rugby tournament. Players (n = 113) voluntarily completed Rugby International Consensus Group 'injury report form'. Descriptive statistics and odds ratios were calculated. A point prevalence of 47 (41.6%) respondents at pre-tournament was found. The tournament recorded 117.6 player-match hours with an incidence of 33 (29.2%) injuries occurring during competition. In contact phase of rugby match, 'being tackled' was associated with a higher number of injuries mostly in the lower limbs. Surface of the playing field was likely to expose a player to injury in pre-competition and during the tournament. Additionally, players who had recurrent previous injuries and oversize gear were more likely to be injured during the tournament. The study showed competition injury incidence similar to that reported in previous studies. Lower limb injuries were most prevalent, especially the ankle while 'getting tackled' during matches. There is a need for an algorithm for injury risk assessment, knee and ankle control training protocol, and use of dynamic knee and ankle supports.

Consensus-Based Best Practice Recommendations for Myelofibrosis Management in Routine Clinical Practice with a Focus on Patients with Cytopenias: Systematic Literature Review and Clinical Practice Recommendations from a Global Consensus Group

Background: Myelofibrosis (MF) is a BCR-ABL1-negative myeloproliferative neoplasm (MPN) characterized by progressive bone marrow fibrosis, splenomegaly, and cytopenias due to impaired hematopoiesis (Passamonti and Mora. Blood 2022). Despite the availability of comprehensive national and international guidelines for diagnosing and managing MF, gaps remain in translating these guidelines into clinical practice, particularly for patients with cytopenias, non-response or intolerance to Janus kinase (JAK) inhibitor treatment, and those ineligible for clinical trial enrollment. Consequently, an international expert consensus group was established with the objective of augmenting the existing guidance. Objectives: To develop a set of evidence- and consensus-based recommendations for managing MF in routine clinical practice, with a focus on patients with cytopenias, including practical strategies and tools to support clinicians. Methods : Modified Delphi methodology was utilized to achieve consensus (Figure 1). A Steering Committee (SC) of 9 expert hematologists (the authors) was established. During an initial meeting, the SC proposed 25 clinical questions that addressed key issues across 5 consensus themes: 1) Defining the thresholds for anemia and when to initiate/modify treatment; 2) defining the threshold for thrombocytopenia and when to initiate/modify treatment; 3) defining JAK inhibitor failure and what would warrant switching treatment; 4) how and when to determine prognosis in patients with MF; and, 5) unmet needs in MF clinical trials. An extended faculty (EF) was then enlisted, comprising hematologists and patient advocacy groups, who voted on the importance of the questions to address. The 15 highest scoring questions were selected for the consensus program (Table 1). To gather scientific evidence around the questions, a systematic literature review (SLR) was conducted using the PubMed and Embase databases, adhering to a PICO (Population, Intervention, Comparison, Outcome) framework. In a subsequent meeting, recommendations were formulated to address the questions using evidence from the SLR and the expert clinical experience of the SC. An online voting platform was then used for both the SC and EF to provide an agreement score for each recommendation. Consensus was achieved when 75% of the respondents agreed within the range of 7-9 on a 9-point scale (1=strongly disagree, 9=strongly agree). Results: Consensus was achieved among voters (hematologists [n=29] and patients [n=9] from Europe, the United States, Canada, Australia, and Israel) for all 15 recommendations. Recommendations in theme 1 emphasize the importance of comprehensive evaluation, exclusion of other causes of anemia, therapy dose optimization, and consideration of additional treatments for managing anemia in patients with MF. Recommendations in theme 2 highlight the complexity of managing splenomegaly, symptoms, and anemia in patients with low platelet counts, and factors guiding therapy selection for these patients. Theme 3 recommendations discuss criteria used to determine JAK inhibitor failure, including relapse, refractoriness, or intolerance, and guidance for distinguishing between these. In theme 4, recommendations address the use of validated prognostic scores at diagnosis and during the disease course, and transplantation risk assessment. The limitations and appropriate utilization of these scores are emphasized, and the need to develop prognostic scores in pre-primary MF is highlighted. Theme 5 recommendations cover the importance of addressing unmet needs in MF clinical trials, and include striving for inclusivity by removing barriers to the participation of underserved patient populations and focusing efforts on validating additional endpoints beyond traditional measures. Conclusions: An international panel of physicians with expertise in MF, together with a diverse EF, was able to achieve a high level of consensus across a wide range of critical gaps in MF management. These recommendations provide a valuable framework to support clinicians in optimizing care for patients with MF.

The Dubai Definition and Diagnostic Criteria of Laryngopharyngeal Reflux: The IFOS Consensus.

The objective of this work was to gather an international consensus group to propose a global definition and diagnostic approach of laryngopharyngeal reflux (LPR) to guide primary care and specialist physicians in the management of LPR. Forty-eight international experts (otolaryngologists, gastroenterologists, surgeons, and physiologists) were included in a modified Delphi process to revise 48 statements about definition, clinical presentation, and diagnostic approaches to LPR. Three voting rounds determined a consensus statement to be acceptable when 80% of experts agreed with a rating of at least 8/10. Votes were anonymous and the analyses of voting rounds were performed by an independent statistician. After the third round, 79.2% of statements (N = 38/48) were approved. LPR was defined as a disease of the upper aerodigestive tract resulting from the direct and/or indirect effects of gastroduodenal content reflux, inducing morphological and/or neurological changes in the upper aerodigestive tract. LPR is associated with recognized non-specific laryngeal and extra-laryngeal symptoms and signs that can be evaluated with validated patient-reported outcome questionnaires and clinical instruments. The hypopharyngeal-esophageal multichannel intraluminal impedance-pH testing can suggest the diagnosis of LPR when there is >1 acid, weakly acid or nonacid hypopharyngeal reflux event in 24 h. A global consensus definition for LPR is presented to improve detection and diagnosis of the disease for otolaryngologists, pulmonologists, gastroenterologists, surgeons, and primary care practitioners. The approved statements are offered to improve collaborative research by adopting common and validated diagnostic approaches to LPR. 5 Laryngoscope, 134:1614-1624, 2024.

New criteria for metabolic dysfunction-associated fatty liver disease: advantage or question? Review

The impact of fatty liver disease on public health and the economics has raised an increased interest in studying this disease. In the year 2020, experts of an international consensus group proposed to rename non‑alcoholic fatty liver disease (NAFLD) to the metabolic dysfunction‑associated fatty liver disease (MAFLD), and to change the diagnostic criteria for the fatty liver disease, because they did not correspond to the recent concepts. The previous name of NAFLD did not fully reflect the pathogenesis of the disease, in which excessive attention was paid to alcohol, and important metabolic risk factors that significantly affect the course of the disease were underestimated. This transition to MAFLD may be appropriate in terms of clinical data, determination of liver steatosis, separation of patients with different MAFLD phenotypes. The new diagnostic criteria for MAFLD are practical, easy to use, and superior to the existing NAFLD criteria for identifying patients at increased risk of developing progressive liver disease. They include evidence of hepatic steatosis, as well as the presence of at least one of three additional criteria: overweight/obesity, type 2 diabetes mellitus, and other metabolic disorders. The limitations of the new criteria for MAFLD include the absence of the concept of non‑alcoholic steatohepatitis, as well as the exclusion from the criteria of MAFLD of subjects with NAFLD without metabolic disorders, who are not diagnosed, and their potential risk may be the cause of future concomitant diseases and complications. However, among the expert society, it was not possible to reach a broad comprehensive understanding regarding the terminology and views on the development of the MAFLD. Debate continues regarding nomenclature and diagnostic criteria for fatty liver disease associated with metabolic dysfunction. Further cohort‑controlled studies based on evidence‑based medicine are needed to resolve controversial issues and to reach a consensus regarding MAFLD. Following up on the disease course and the evolution of medical terms can improve the understanding of the pathophysiology of liver diseases and create a new concept of fatty liver disease. Coordination of views of international experts in the field of the study of MAFLD will have a decisive role in the promotion of clinical practice and research.

NAFLD renaming to MAFLD, MASLD: background, similarities, differences, and countermeasures

Nonalcoholic fatty liver disease (NAFLD) is a chronic metabolic stress liver injury due to chronic malnutrition in genetically susceptible individuals. With the prevalence of obesity, diabetes, and metabolic syndrome, NAFLD has become the world's number one chronic liver disease, and the flaws of forty years of exclusive disease diagnostic criteria and stigmatized disease terminology are becoming increasingly prominent. To this end, in the past three years, the international consensus group and the three major hepatology societies have suggested that NAFLD be renamed metabolism-associated fatty liver disease (MAFLD) and metabolism-associated steatosis liver disease (MASLD). Here is a description of the background of naming NAFLD, MAFLD, and MASLD, the similarities and differences of the three terms, the existing disputes, and our country's coping strategies.

HOST FACTORS AND RISK OF PIN SITE INFECTION IN EXTERNAL FIXATION: A LITERATURE REVIEW EXAMINING AGE, BODY MASS INDEX, SMOKING, AND COMORBIDITIES INCLUDING DIABETES

An international Consensus Group has by a Delphi approach identified the topic of host factors affecting pin site infection to be one of the top 10 priorities in external fixator management. The aim of this study was to report the frequency of studies reporting on specific host factors as a significant association with pin site infection. Host factors to be assessed was: age, smoking, BMI and any comorbidity, diabetes, in particular. The intention was an ethological review, data was extracted if feasible, however no meta-analysis was performed.A systematic literature search was performed according to the PRISMA-guidelines. The protocol was registered before data extraction in PROSPERO. The search string was based on the PICO criterias. A logic grid with key concept and index terms was made. A search string was built assisted by a librarian. The literature search was executed in three electronic bibliographic databases, including Embase MEDLINE (1111 hits) and CINAHL (2066 hits) via Ovid and Cochrane Library CENTRAL (387 hits). Inclusion criteria: external fixation, &gt;1 pin site infection, host factor of interest, peer-reviewed journal. Exclusion criteria: Not written in English, German, Danish, Swedish, or Norwegian, animal or cadaveric studies, location on head, neck, spine, cranium or thorax, editorials or conference abstract. The screening process was done using Covidence.A total of 3564 titles found. 3162 excluded by title and abstract screening. 140 assessed for full text eligibility. 11 studies included for data extraction. The included studies all had a retrospective design. Three identified as case-control studies. Generally the included studies was assessed to have a high risk of bias. A significant associations between pin site infection for following host factors: a) increased HbA1C level in diabetic patients; b) congestive heart failure in diabetic patients; c) less co-morbidity; d) preoperative osteomyelitis was found individually.This systematic literature search identified a surprisingly low number of studies examining for risk of pin site infection and host factors. Thus, this review most of all serves to demonstrate a gap of evidence about correlation between host factors and risk of pin site infection, and further studies are warranted.

Degenerative cervical myelopathy: Where have we been? Where are we now? Where are we going?

Degenerative cervical myelopathy (DCM), a recently coined term, encompasses a group of age-related and genetically associated pathologies that affect the cervical spine, including cervical spondylotic myelopathy and ossification of the posterior longitudinal ligament (OPLL). Given the significant contribution of DCM to global disease and disability, there are worldwide efforts to promote research and innovation in this area. An AO Spine effort termed 'RECODE-DCM' was initiated to create an international multistakeholder consensus group, involving patients, caregivers, physicians and researchers, to focus on launching actionable discourse on DCM. In order to improve the management, treatment and results for DCM, the RECODE-DCM consensus group recently identified ten priority areas for translational research.The current article summarizes recent advancements in the field of DCM. We first discuss the comprehensive definition recently refined by the RECODE-DCM group, including steps taken to arrive at this definition and the supporting rationale. We then provide an overview of the recent advancements in our understanding of the pathophysiology of DCM and modalities to clinically assess and diagnose DCM. A focus will be set on advanced imaging techniques that may offer the opportunity to improve characterization and diagnosis of DCM. A summary of treatment modalities, including surgical and nonoperative options, is then provided along with future neuroprotective and neuroregenerative strategies. This review concludes with final remarks pertaining to the genetics involved in DCM and the opportunity to leverage this knowledge toward a personalized medicine approach.

Validation of the International Consensus Group Criteria for Slide Review Following Automated Complete Blood Count at Jimma Medical Center, Ethiopia.

The international consensus group suggested criteria for action following automated complete blood count and white blood cell differential analysis. These criteria were set based on data from laboratories of developed countries. It is highly important to validate the criteria in developing countries where infectious diseases are still rampant that can affect blood cell count and morphology. Thus, this study aimed to validate the consensus group criteria for slide review at Jimma Medical Center, Ethiopia from November 1, 2020 to February 30, 2021. The study comprised a total of 1685 patient samples from the daily laboratory workload of CBC analysis. The samples were collected in K2-EDTA tubes (Becton Dickinson) and analyzed using Coulter DxH 800 and Sysmex XT-1880 hematology analyzers. A slide review was done on two Wright-stained slides for each sample. All statistical analyses were performed using SPSS version 20 software. There were 39.8% positive findings, the majority of which were related to red blood cells. The false negative and false positive rates for Sysmex and Coulter analyzer were 2.4% vs 4.8%; and 4.6% vs 4.7%, respectively. The false negative rate was unacceptably higher when we used physicians' triggered slide review, which was 17.3% and 17.9% for Sysmex and Coulter analyzers, respectively. Generally, the consensus group rules are suitable to use in our setting. However, we might still need to modify the rules, particularly to reduce the review rates. It is also necessary to confirm the rules with case mixes proportionally derived from the source population.

Pediatric combined hepatocellular-cholangiocarcinoma (cHCC-CC) with neuroendocrine features: distinguishing genetic alterations detected by chromosomal microarray

BackgroundLiver tumors exhibiting hepatocellular, cholangiocarcinoma, and neuroendocrine features are extremely rare, with only five cases reported in the literature.Case presentationWe present an unusual case of a combined hepatocellular-cholangiocarcinoma (cHCC-CC) with neuroendocrine features in a pediatric patient. A 16-year-old presented with abdominal pain and a 21.0 cm mass in the right hepatic lobe with extension into the left lobe. Histology showed a poorly differentiated tumor with a solid, tubuloglandular, and microcystic architecture. Immunohistochemistry results were negative for hepatic markers, positive for markers of biliary differentiation, and positive for neuroendocrine differentiation. The neoplasm was reviewed at several institutions with differing diagnoses. Single nucleotide polymorphism (SNP) chromosomal microarray (CMA) showed large deletions within chromosomes 6q and 13q in both the hepatocellular-like areas and the cholangiocarcinoma-like areas, with additional large deletions in the cholangiocarcinoma-like areas, supporting origin from hepatocellular carcinoma. The final diagnosis was a cHCC-CC with neuroendocrine features.ConclusionsDiagnosis of cHCC-CCs relies predominately on histomorphology, as per the 2018 International Consensus Group on the nomenclature of cHCC-CC. These findings in this case support that the pathological classification of these lesions be based on molecular data, which could better direct treatment. Further classification of cHCC-CCs and determination of their clinicopathological relevance will require more interobserver consistency and continued molecular profiling of these lesions.

Drug-coated balloon-only strategy for percutaneous coronary intervention of de novo left main coronary artery disease: the importance of proper lesion preparation.

This retrospective single-center registry study included all consecutive patients who underwent percutaneous coronary intervention (PCI) for a de novo left main coronary artery lesion using drug coated-balloon (DCB)-only strategy between August 2011 and December 2018. To best of our knowledge, no previous studies of DCB-only strategy of treating de novo left main coronary artery disease, exist. The primary endpoint was major adverse cardiovascular events (MACEs) including cardiac death, non-fatal myocardial infarction, and target lesion revascularization (TLR). The cohort was divided into two groups depending on weather the lesion preparation was done according to the international consensus group guidelines. Sixty-six patients (mean age 75±8.6, 72% male), 52% of whom had acute coronary syndrome, underwent left main PCI with the DCB-only strategy. No procedural mortality and no acute closures of the treated left main occurred. At 12 months, MACE and TLR occurred in 24% and 6% of the whole cohort, respectively. If the lesion preparation was done according to the guidelines, the MACE and TLR rates were 21.2% and 1.9%. Left main PCI with the DCB only-strategy is safe leading to acceptable MACE and low TLR rates at one year, if the lesion preparation is done according to the guidelines.

Disparities in Somatic Mutations and Outcomes in Primary Central Nervous System Lymphoma Comparing Patients of Hispanic and Non-Hispanic Ethnicity

Background: Primary central nervous system lymphoma (PCNSL) is characterized by frequent MYD88 L265P activating mutations, biallelic CDKN2A loss, and mutations in CD79B, PIM1, and CARD11. However, the extent to which mutations vary by ethnicity is unknown. The purpose of this study is to describe differences in genetic mutations and survival between PCNSL patients of different ethnicities. Methods: We retrospectively analyzed patients ≥ 18 years with PCNSL diagnosed between January 2011- December 2020 and treated at UCSF-Fresno and University of Oklahoma. Next generation sequencing was performed on Formalin Fixed Paraffin Embedded tissue. We examined mutations in 434 genes by DNA analysis and 1408 genes by RNA analysis. Sequencing was performed using an Illumina NextSeq 550 system platform. The clinical data including age, sex, ethnicity, race, ECOG performance status, number and location of lesions, HIV status, LDH, protein in the CSF, and treatment regimens were reviewed. Treatment response was assessed by MRI using the international consensus group response criteria. Comparison of patient characteristics and rate of genetic alterations between Hispanic and Non-Hispanic patients was done using the Fisher exact test or Chi-square test. Time-to-event analyses were conducted using the Kaplan-Meier method and were compared by a log-rank test. Univariate analyses were performed via the Cox proportional hazards model. Analysis was performed with STATA version 16.0. Results: Among the 51 patients analyzed, the median age was 61. 54% were males and 43% were Hispanic. 13% had HIV, 27% had deep brain involvement, and 58% had non-germinal center (non-GC) type per Hans Criteria. 81% of Hispanic patients had non-GC vs 41% non-Hispanic (P=0.006). There was no statistically significant difference in age, performance status, HIV status, deep brain involvement, or CSF involvement between Hispanic non-Hispanic patients. 90% of patients received systemic chemotherapy for initial treatment, with 41% receiving high dose Methotrexate, Rituximab and Temozolomide. No patients received autologous stem cell transplant in first remission. 90% Hispanic Vs 89% Non-Hispanic received systemic chemotherapy (P=0.447). 29 patients (56%) achieved complete response (CR)/unconfirmed complete response (CRu). 2-year progression-free survival (PFS) was 67.4%, and 2-year overall survival (OS) was 55% for all patients. 177 genetic alterations were detected with the most common being MYD88, CD79B, TET2, PIM1, ETV6 and TP53 (table). Hispanic patients, compared with non-Hispanic patients, had a lower rate of MYD88 mutation (40.9% vs 72.4%, P=0.024) and TP53 mutation (0.0% vs 24.1%, P=0.001). 2-year PFS in Hispanics was 40% vs 30% in non-Hispanics (P=0.526) and 2-year OS in Hispanics was 0.63% vs 0.33% in non-Hispanics (P=0.05). In univariate analysis, age and genetic alterations (MYD88, CD79B, TET2, PIM1 and ETV6) were not associated with significant differences in 2-year PFS or OS. Performance status (ECOG ≤ 2), negative CSF cytology, and treatment with multi-agent chemotherapy rather than high dose Methotrexate alone were associated with better 2-yr OS. Conclusions: We identified highly recurrent genetic alterations in PCNSL. Our data suggest that some heterogeneity in the most frequent mutations in PCNSL may be related to ethnicity. Hispanic patients in our study have better 2-year OS; however, the data is limited by the retrospective analysis and the small patient number. Further studies on a larger patient population are warranted to evaluate genetic heterogeneity in different ethnic groups and effect of ethnicity and socio- economic status on outcomes in patients with PCNSL Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Managing Shoulder Instability in the Overhead Athlete.

Shoulder instability in the overhead athlete is a difficult problem because of the balance between necessary laxity for athletic movements and stability of the joint. The purpose of this review is to provide an overview of the clinical evaluation of shoulder instability in the overhead athlete and present evidence-based management strategies for each subtype of shoulder instability, including novel techniques and outcomes. Recent investigation has shown that throwers and other overhead athletes are more likely to present with subtle subluxation events rather than discrete dislocations as their primary symptom. While overhead athletes with discrete anterior dislocation events are likely to begin with non-operative management, many progress on to surgical intervention. Surgical management of glenohumeral joint instability continues to pose challenges due to the potential for over-tensioning for the sake of stability at the expense of the adaptive laxity that often confers performance benefits in the overhead athlete. Novel, individualized, and sport/position specific approaches are needed to address this complex issue. The optimal management of shoulder instability in the overhead athlete continues to be a controversial topic due to the complex work-up, an increasing number of surgical options with varying indications, and low volume of high-quality studies comparing any of the treatment options. The Anterior Shoulder Instability International Consensus Group guidelines from February 2022 offer the most updated guidelines on work-up and management. Overall, high-quality randomized controlled trials are required to determine the optimal treatment for specific pathologies and aid in creating patient-centered management plans.