Larson, Dirk

ABSTRACT Based on anecdotal observation of fatty infiltration (FI) of the opponens pollicis (OPP) muscle in patients with thumb carpometacarpal (CMC) Osteoarthritis (OA), we sought to examine the association of FI with CMC OA. We reviewed 747 consecutive 3 T wrist magnetic resonance imaging (MRI) studies for evidence of FI in the thenar muscles. This population was divided into two cohorts based on radiographic analysis: a cohort without thumb CMC OA ( n = 440) and a second cohort with thumb CMC OA ( n = 307), staged according to the Eaton–Littler classification. Statistical analysis using logistic regression was performed to investigate clinical factors associated with the presence of FI in the thenar muscles. FI was present in 133 patients with CMC OA (43.3%). FI, when present, was located only in the OPP. We found no OPP FI in the cohort without CMC OA (440 patients). Among patients with CMC OA, increasing age, male sex and advanced OA stage were significantly associated with the presence of OPP FI. OPP FI is a frequent finding in CMC OA. This FI could affect the biomechanical function of the OPP. In the future, we plan to analyze clinical outcomes in CMC OA patients with and without FI, and more focused in vivo studies of OPP function. OPP FI could potentially affect the function and the stability of the thumb CMC joint in patients with CMC OA. Orthopaedic Research Society. Journal of Orthopaedic Research® 00:00–00, 2026.

Abstract Background Patients with Inflammatory Bowel Diseases (IBD) are at higher risk of developing dysplastic lesions and colorectal cancer (CRC). Despite the use of high-definition endoscopes, dysplasia is not always detected at colonoscopy. This study aims to determine the rate of dysplastic lesions detected only at colectomy in IBD patients and to identify the characteristics of patients with undetected dysplasia. Methods We retrospectively identified IBD patients that underwent total or sub-total colectomy at Mayo Clinic, between January 2013 and December 2022. Patients with a confirmed IBD diagnosis, with at least one colonoscopy report prior to surgery available, were included. Data collected was demographics, comorbid conditions, colonoscopy, surgery, and their pathology reports. Concordance between dysplasia found at colonoscopy and dysplasia found at surgery was evaluated, noting dysplasia sites and grade. Patients were then divided into three groups: those with at least one undetected dysplastic lesion at surgery, those with dysplasia detected at colonoscopy and no further lesions at surgery, and those without dysplasia at both. Results Seven hundred-four patients were included: 387 (55%) were male, 450 (64%) had ulcerative colitis, 197 (28%) had Crohn’s disease and 57 (8%) had indeterminate colitis. In 42 patients (6%) dysplasia was undetected at colonoscopy, 136 (19.3%) had dysplasia detected at colonoscopy, and 526 (74.7%) had no dysplasia at both. In the group with dysplasia detected, 40 patients (30%) had dysplasia only at colonoscopy while 96 (70%) had dysplasia at surgery as well. Among those with undetected dysplasia, in 17 (40%) dysplasia was identified only at surgery: 14 (82%) had low grade dysplasia and 3 (18%) had cancer. All cancers were stage 1. Three of these patients (18%) had primary sclerosing cholangitis and 4 (23%) had a family history of cancer. In the other 25 patients (60%), dysplasia was detected at colonoscopy but further dysplastic foci were identified at surgery. In 13 (52%) patients dysplasia was upgraded, in 2 (8%) was downgraded and in 10 (40%) the grade was confirmed. Compared to those with detected dysplasia, these patients more frequently had moderate-severe disease activity, and less frequently a prior history of dysplasia. There was no difference in age at surgery, but those with undetected dysplasia had less years of disease at colectomy. Further results are shown in Table 1. Conclusion The rate of dysplastic lesions found at colectomy and missed at colonoscopy is 6%. Dysplastic lesions tend to be undetected when endoscopic disease activity is more severe and regardless of the use of extensive nontargeted biopsies.

Abstract Background Minimally invasive surgery (MIS) is the first-line approach for ileocolic resection in patients with Crohn’s disease (CD) and it is safe and feasible even in complex cases. However, an open approach is still required, but indications to open ileocolic resection for CD are not well described. Methods All consecutive adult patients with CD who underwent elective ileocolic resection in the Departments of Colon and Rectal Surgery at Mayo Clinic Rochester, Minnesota and Jacksonville, Florida between September 2014 and March 2021 were included and divided into “open” and “MIS” groups. Open approach was defined as upfront laparotomy, MIS included laparoscopic and robotic approaches, and conversion was defined as incision made earlier than planned. Indications to open approach were retrospectively reviewed by two authors, and any incongruity was resolved. Analogous indications were also assessed in the MIS group, as appropriate. Indications, baseline, perioperative characteristics, and short-term postoperative outcomes were compared between open and MIS. Results Among 319 ileocolic resections for CD, 45 (14.1%) were open and 274 (85.9%) MIS. Indications for open approach were severe disease, adhesions at previous surgery, history of abdominal sepsis, multifocal and extensive disease, abdominal wall involvement, concomitant open procedures, small bowel dilatation, and anaesthesiologic contraindications (Table 1). In addition, two or more of the above indications were present in 40 patients (89%) in the open group, while only in 6 patients (2%) in the MIS group (p<0.001). Compared to MIS patients, patients undergoing open ileocolic resection were older, with longer CD duration, more previous surgery and preoperative intra-abdominal abscess drainage (Table 2). Nine patients were converted in the MIS group (3.3%). Intraoperatively, open group had more adhesiolysis ≥45 min, more intraoperative complications, more blood loss, more primary stoma, less anastomosis, and longer operative time (Table 3). Postoperatively, they had more overall postoperative complications, ileus, surgical site infections, dehydration, vascular thromboembolism, higher severity by Clavien-Dindo classification, and longer length of stay (Table 4). Conclusion Overall rate of open approach ileocolic resection for CD was 14 % during a 7-years period in a referral centre. Open approach was the only operation performed in cases of abdominal wall involvement, concomitant open procedures, and anaesthesiologic contraindication. In addition, the presence of at least two indications,predicting high technical complexity, may be considered as a no-go for the MIS approach in ileocolic resections for CD.

SummaryPatients with asymptomatic/smouldering Waldenström macroglobulinaemia (SWM) have a variable risk of progression to active WM. Our study evaluated 143 patients with SWM consecutively seen between January 1996 and December 2013. With a median [95% confidence interval (CI)] follow‐up of 9·5 [8·1–11·5] years, the cumulative rate of progression was 11% at 1 year, 38% at 3 years and 55% at 5 years. On multivariate analysis, haemoglobin (Hb) ≤123 g/l [risk ratio (RR) 2·08; P = 0·009] and β2‐microglobulin (β2M) ≥2·7 µg/ml (RR 2·0; P = 0·01) were independent predictors of a shorter time‐to‐progression (TTP) to active WM. Patients with myeloid differentiation factor 88 wild type (MYD88WT) genotype (n = 11) demonstrated a trend toward shorter TTP [median (95% CI) 1·7 (0·7–8·7) vs. 4·7 (2·4–7·7) years for the MYD88L265P cohort, n = 42; P = 0·11]. The presence of C‐X‐C chemokine receptor type 4 (CXCR4) mutation (n = 29) did not impact the TTP (median: 3 years for CXCR4WT vs. 5·6 years for CXCR4MUT, P = 0·34). The overall survival (OS) for patients with SWM (median: 18·1 years) was comparable to an age‐, sex‐ and calendar year‐matched USA population (median: 20·3 years, P = 0·502). In conclusion, Hb and β2M at diagnosis represent independent predictors of progression to active WM. Comparable survival of SWM and a matched USA population argues against pre‐emptive intervention in this patient population.

Abstract Background: Clonal cytogenetic aberrations define multiple myeloma (MM) into unique subsets of the disease each one with unique clinical and biologic features, associations with laboratory and pathologic markers and presumed differential influence on disease progression. While it is widely accepted that translocations represent primordial events in the pathogenesis of MM, it is controversial whether all translocations can be associated with disease stability and non-malignant behavior (i.e. in MGUS/SMM). We have found the translocations in cases of MGUS using dual fusion, cIg enhanced, interphase FISH, while others have found this translocation at lower prevalence using single fusion interphase FISH or the RT-PCR for IgH/MMSET. We thus sought to clarify by expanding the study of the t(4;14) among patients with MGUS and SMM. Materials and methods: We studied 210 patients who had the diagnosis of MGUS and SMM and entered into the Mayo Clinic Dysproteinemia database. Patients were excluded if they had active MM, extramedullary disease or plasmacytoma. Patients with isolated lytic bone lesions could be included if they had no overt evidence of progression. All studied patients had provided written informed consent for the collection of a research bone marrow aliquot that was collected at the time of routine bone marrow procurement. All patients had cytospin slides that were studied for a t(4;14) using cIg-FISH as previously described by us and using a double fusion FISH strategy. The importance of this is that the strategy will detect unbalanced t(4;14) with loss of der(14). Results: Twenty patients (9.5%) had evidence of the chromosome translocation. Detailed demographic data was available in 19; 14 were women (74%), 13 of 19 (68%) had SMM and there was no bias for heavy chain IgA (26%). Patients with t(4;14) were slightly younger than those without the abnormality (52 vs. 61 years), had similar hemoglobin concentrations, had slightly higher concentration of the serum M spike (2.0 vs 1.75 g/dl) and had overall slightly higher bone marrow plasmacytosis (median 23% vs 10%). Patients were followed since diagnosis for a median of 33 months (range 2–162 months). Three patients progressed to active MM at 12, 12 and 26 months after original diagnosis (all three originally having indolent/SMM). Conclusion: The t(4;14) can occur in patients with MGUS and SMM and without evidence of progression to MM. The prevalence is similar to that observed in MM, albeit slightly lower (9.5% versus 14%). In most “benign” plasma cell neoplasms the translocation is associated with greater plasmacytosis and thus enriched for in the smoldering MM category. It is also likely that the t(4;14) confers a higher risk of progression to MM given; a) its enrichment in SMM, b) the slightly higher prevalence of the translocation in MM as opposed to MGUS/SMM, and c) the well documented aggressive clinical course of MM with t(4;14).

Abstract Background: Immunoglobulin free light chains (FLC) form the substrate for synthesis of amyloid fibrils in patients with AL amyloidosis. Development of FLC assay (Freelite) has allowed us to better assess the clonal cell burden in patients with AL amyloid. The relationship of the light chain types and their levels in serum to the clinical feature at presentation and the eventual outcome has not been systematically studied. Methods: We identified 730 patients with biopsy proven AL amyloidosis, who were seen at Mayo Clinic between January 1980 and July 2006, who were seen within 90 days of their diagnosis and in whom FLC levels were performed or had stored serum available for analysis. Cardiac biomarkers (cTnT, NT ProBNP) were also performed on stored serum for some of the patients as part of previous studies. Clinical data and follow up status are prospectively collected into the Dysproteinemia database, which was used for the study. Results: The median age of the study population was 63 years (range; 32–90) and 463 patients (63%) were male. The median estimated survival for the entire group was 37 months from diagnosis and the median follow up for the 263 patients (37%) alive at the time of the analysis was 27.8 months (range; 1–177 months). The plasma cell clone was lambda in 528 patients (72%) and kappa in 202 (28%) patients. The median absolute difference between the FLCs was 19.6 mg/dL for the entire group (range; 0.01–2478); for the kappa patients was 29.4 mg/dL (range; 0.01–1359) and for the lambda patients was 18.2 mg/dL (range; 0.03–2478). Kappa AL was associated with more involvement of the GI tract and liver as indicated by higher alkaline phosphatase (1.8 vs. 1.3 fold; P=0.03), higher total bilirubin (0.95 vs. 0.78 mg/dL, P = 0.04) and lower serum carotene (119 vs. 155 ug/dL; P = 0.0002). On the contrary, renal involvement was more in the lambda AL with the 24 hour urinary albumin higher in the lambda AL (2.4 gm vs. 1.4 gm; P = 0.0002) and lower serum albumin (2.77 vs. 2.97 mg/dL; P = 0.001). While there was no difference in the overall survival (OS) between the kappa and lambda AL, the median OS for those without a heavy chain was significantly shorter (12.6 months vs. 29.9 months; P= 0.01) compared to those with a heavy chain identified. There was also a correlation between high FLC difference and degree of organ involvement, especially cardiac. Among the 202 kappa AL patients, the median survival for those with a high FLC difference ( > 29.4 mg/dL) was 13 months vs. 48.8 months for those with low difference (P = 0.001). Similarly among the 528 patients with lambda AL, those with high difference (> 18.2 mg/dL) had a median OS of 9.3 months compared to 33 months for those with low difference (P < 0.0001) (Figure). The FLC difference was independent of the cTnT, NT Pro BNP, uric acid and fold-increase in alkaline phosphatase, all of which were significant in the multivariable analysis. Conclusions: The type of FLC impacts the spectrum of organ involvement, with gastrointestinal involvement observed more frequently with kappa, and renal involvement with lambda FLC. The FLC burden correlates with the degree of organ involvement, and is a significant predictor of overall survival in AL amyloidosis. Lambda FLC exerts similar effect as kappa FLCs, but at lower levels confirming the increased “amyloidogenicity” of lambda FLC. Finally, lack of a chaperone heavy chain is associated with a poorer outcome. Figure 1. Overall survival form diagnosis in patients with high vs. low FLC difference (using median values for cutoffs for kappa and lambda FLC) Figure 1. Overall survival form diagnosis in patients with high vs. low FLC difference (using median values for cutoffs for kappa and lambda FLC)

Abstract Abstract 3980 Background: Nearly half of patients with multiple myeloma (MM) are over 70 years at the time of diagnosis. While the survival of patients with myeloma has improved in the last decade, several studies have suggested no significant change for the elderly patients. These patients often have other comorbidities and are less likely to tolerate standard treatment approaches. We retrospectively studied the treatment patterns, outcomes, and prognostic factors in patients over 75 years of age. PATIENTS AND METHODS: We identified 212 patients who were older than 75 years from among 1545 patients seen at the Mayo Clinic within 90 days of diagnosis during 1999 to 2008. We only included 139 patients in whom complete treatment details were available. RESULTS: The median age was 80 years (range: 76–94) with 20 (14%) patients older than 85 years; 79 (57%) were male. Thirty-five patients (25%) had a history or coexistence of one or more malignancies. Chromosome analysis and FISH were performed in 65% and 22% respectively. Abnormal cytogenetics were seen in 30 (33%) of the 90 tested patients. The median survival of the 139 elderly patients was 27 months (95% CI: 20∼35) compared to 62 months (56∼68) for 1,290 patients ≤ 75 years of age seen during the same period. Sixty-nine (50%) patients received one or more novel agents (thalidomide, lenalidomide, pomalidomide, bortezomib) and showed longer median survival (40 months vs 13 months) compared with those not receiving these agents (p=0.0008). Age over 85, initial poor performance score > 1, thrombocytopenia, elevated serum LDH or beta2-microglobulin, response more than stable disease to first therapy resulted in inferior survival. Among them, only performance status had the persistent significance in multivariate analysis. CONCLUSION: Older patients receiving newer therapies appear to have a better outcome, which is still lagging behind the younger patients. A poor performance score at diagnosis predicts for eventual poor outcome. Disclosures: No relevant conflicts of interest to declare.

Abstract Background: FLC is a valuable diagnostic tool to monitor response in patients with AL and oligosecretory MM. It is also prognostic in patients with MGUS. Its value in patients with non-oligosecretory myeloma has not been defined. Because of the short half-life of free-light chains, an early drop in free-light chain might be predictive for long term outcome post PBSCT. Methods: Between 8/1/03 and 12/10/04, 45 patients with multiple myeloma and abnormal FLC ratios (less than 02.6 or greater 1.65), who were undergoing PBSCT consented to have waste serum from routine post-transplant daily blood draws collected and frozen for future FLC analysis. The immunoglobulin FLC assay (Binding Site, U.K.) was run on samples collected from day +1 until patients were dismissed from our transplant center. Hematologic response was coded according to standard IBMTR criteria at approximately 3 months status post transplant (BJH 1998). Two types of immunoglobulin FLC response were coded: 50% reduction (FLC50) and 90% reduction (FLC90) of the difference of the involved and uninvolved FLC (Leukemia 2006). Two time periods of FLC response were analyzed: early (day 7); and delayed (day 19, range 13 to 24). Endpoints analyzed were overall response (>=PR), complete response rate (CR), progression free survival (PFS), and overall survival (OS). Results: The median age of the myeloma group was 59 years, and 53% were male. Thirty-three patients were monoclonal kappa, and 12 lambda. Forty-two percent were transplanted in response/plateau, 22% were primary refractory, and 36% relapsed disease. The overall hematologic response rate was 93% with a CR rate of 33%. Twenty-five patients have relapsed at a median of 14.2 months. Twelve patients have died, and median overall survival for the group has not been reached at a median follow-up of 24.6 months. Forty-nine and 58 percent of patients had early and delayed FLC90, respectively. Early FLC90, but not delayed FLC90, predicted for complete response (p<0.001). Neither early nor delayed FLC90 predicted for either PFS or OS. In addition, 89% and 96% of patients had an early and delayed FLC50, respectively. FLC50 at either time point did not predict for overall response, CR, PFS, or OS. Conclusion: Immunoglobulin free light chain responses are seen within the first weeks post high dose chemotherapy with peripheral blood stem cell transplant. A 90% reduction in FLC seen within the first seven days predicts for complete response. However, this does not yet translate into prolonged PFS or OS, but with longer follow-up separation of the survival curves may be seen.

Background/aim To determine if Boys Bantam and Peewee and Girls U14 sustain fewer concussions, head hits, ‘other injuries’ and penalties in hockey tournaments governed by intensified fair play (IFP) than non-intensified fair play (NIFP). Methods A prospective comparison of IFP, a behaviour modification programme that promotes sportsmanship, versus control (non-intensified, NIFP) effects on numbers of diagnosed concussions, head hits without diagnosed concussion (HHWDC), ‘other injuries’, number of penalties and fair play points (FPPs). 1514 players, ages 11–14 years, in 6 IFP (N=950) and 5 NIFP (N=564) tournaments were studied. Results Two diagnosed concussions, four HHWDC, and six ‘other injuries’ occurred in IFP tournaments compared to one concussion, eight HHWDC and five ‘other injuries’ in NIFP. There were significantly fewer HHWDC in IFP than NIFP (p=0.018). However, diagnosed concussions, ‘other injuries’, penalties and FPPs did not differ significantly between conditions. In IFP, a minority of teams forfeited the majority of FPPs. Most diagnosed concussions, HHWDC, and other injuries occurred to Bantam B players and usually in penalised teams that forfeited their FPPs. Conclusions In response to significant differences in HHWDC between IFP and NIFP tournaments, the following considerations are encouraged: mandatory implementation of fair play in regular season and tournaments, empowering tournament directors to not accept heavily penalised teams, and introducing ‘no body checking’ in Bantam.