Gliovascular transcriptional perturbations in Alzheimer's disease reveal molecular mechanisms of blood brain barrier dysfunction.

To uncover molecular changes underlying blood-brain-barrier dysfunction in Alzheimer's disease, we performed single nucleus RNA sequencing in 24 Alzheimer's disease and control brains and focused on vascular and astrocyte clusters as main cell types of blood-brain-barrier gliovascular-unit. The majority of the vascular transcriptional changes were in pericytes. Of the vascular molecular targets predicted to interact with astrocytic ligands, SMAD3, upregulated in Alzheimer's disease pericytes, has the highest number of ligands including VEGFA, downregulated in Alzheimer's disease astrocytes. We validated these findings with external datasets comprising 4,730 pericyte and 150,664 astrocyte nuclei. Blood SMAD3 levels are associated with Alzheimer's disease-related neuroimaging outcomes. We determined inverse relationships between pericytic SMAD3 and astrocytic VEGFA in human iPSC and zebrafish models. Here, we detect vast transcriptome changes in Alzheimer's disease at the gliovascular-unit, prioritize perturbed pericytic SMAD3-astrocytic VEGFA interactions, and validate these in cross-species models to provide a molecular mechanism of blood-brain-barrier disintegrity in Alzheimer's disease.

Evaluation of Platelet-rich Plasma and Microneedling for Facial Skin Rejuvenation.

Background: The regenerative properties of platelet growth factors make platelet-rich-plasma (PRP) an attractive modality for treatment of aging skin. The main objective of this study was to determine efficacy and safety of PRP injections and microneedling compared with saline injections in women with aging skin of the face. Methods: In this prospective, randomized clinical trial, 18 women with facial aging were randomized to receive either PRP injections to the unilateral face and saline injections to the contralateral side, or vice versa. Microneedling was performed after injections on the entire face. Physician assessment, photographs, and treatment satisfaction questionnaires were used for outcome assessment at baseline and 16- and 24-week follow-ups. Results: There was no evidence of improvement and suggestion of worsening in skin laxity and rhytides from baseline to weeks 4, 16, and 24 for PRP and saline (all P ≤ 0.004) and no notable difference in skin roughness between baseline and follow-up time points for PRP or saline (all P ≥ 0.19). The degree of change in skin laxity, rhytides, and skin roughness from baseline to follow-up time points was similar for PRP and saline. All patients experienced some degree of pain/discomfort and burning/stinging sensation at treatment weeks 4, 8, and 12 for both saline and PRP. Conclusions: PRP injections did not seem to be effective for treatment of aging skin of the face in women, with no notable macroscopic improvement in appearance when compared with baseline or saline injections. Advanced age of study participants (>45 years) and less-sensitive methods of evaluation may be potential contributing factors to the lack of detected response.

Total Knee Arthroplasty With and Without Schedule II Opioids: A Randomized, Double-Blinded, Placebo-Controlled Trial.

INTRODUCTION: Orthopedic surgeons are the third highest prescribers of narcotics. Previous work demonstrated that surgeons prescribe three times the narcotics required, and most patients do not properly dispose of leftover medication following surgery. This has prompted the creation of multimodal pain regimens to reduce reliance on narcotics. It is unknown if these pathways can effectively eliminate opioids following total knee arthroplasty (TKA). Our purpose was to evaluate a multimodal regimen without schedule II narcotics following TKA, in a randomized, blinded fashion. We hypothesized that there would be no difference in pain scores between groups. METHODS: A total of 43 narcotic-naïve patients participated in a randomized, double-blinded, placebo-controlled trial. Postoperative protocols were identical between cohorts, except for the study medication. The narcotic group received an encapsulated 5 mg oxycodone, whereas the control group received an encapsulated placebo. Perioperative outcomes were compared with routine statistical analysis. RESULTS: Four patients withdrew early secondary to pain: three in the placebo group and one in the narcotic group (p=1.00). We found no difference in hospital length of stay (p=0.09) or pain scores at all time points between cohorts (all p>0.05). There was a higher proportion of patients using a narcotic in the opioid treatment arm at day 30 (40% vs. 21.4%, p=0.29) and day 60 (20% vs. 7.1%, p=0.32), although this was not statistically significant. CONCLUSION: A multimodal regimen without schedule II narcotics demonstrates equivalent pain scores and may reduce the risk of long-term opioid dependence following TKA.

A prospective study of the relationship between illness perception, depression, anxiety, and quality of life in hematopoietic stem cell transplant patients.

AIM: The aim of study was to investigate whether depression and anxiety symptoms and illness perception prior to hematopoietic stem cell transplantation (HSCT) predict health related quality of life (HRQOL) at Day 100 and 1 year following HSCT. METHODS: A total of 205 patients who underwent HSCT (N = 127 autologous transplants, N = 78 allogeneic transplants) were included in this prospective study. Baseline assessment was assessed prior to transplantation and post HSCT data were collected at Day 100 and 1 year. At baseline we assessed depressive symptoms (Patient Health Questionnaire-9), anxiety symptoms (Generalized Anxiety Disorder-7), illness perception (Brief Illness Perception Questionnaire), and HRQOL (Functional Assessment of Cancer Therapy-BMT). RESULTS: Patients who expressed a greater level of concern about the severity, course, and ability to exert control over one's illness (i.e., illness perception) and who reported a greater level of depression and anxiety symptoms prior to HSCT reported lower HRQOL at both Day 100 and 1 year posttransplant, with a similar degree of association observed at the two follow-up time points. CONCLUSIONS: Our findings suggest that pretransplant perceptions about their illness and negative mood are significant predictors of HRQOL following HSCT. Illness perception, depression, and anxiety are potentially modifiable risk factors for less than optimal outcome after HCSCT and intervention strategies should be explored.

Loneliness, immunological recovery patterns, and health-related quality of life (HRQOL) outcomes in patients receiving hematopoietic stem cell transplantation.

PURPOSE: Loneliness may compromise health-related quality of life (HRQOL) outcomes and the immunological impacts of loneliness via neuroendocrinological mechanisms likely have consequences for patients who have undergone a hematopoietic stem cell transplantation (HSCT). RESEARCH APPROACH AND MEASURES: Loneliness (pre-transplant), immunological recovery (Day 30, Day 100, 1-year post-transplant), and HRQOL (Day 100, 1 year) were measured in a sample of 205 patients completing a HSCT (127 autologous, 78 allogenic). RESULTS: Greater levels of pre-transplant loneliness predicted poorer HRQOL at Day 100 and 1-year follow-up. Loneliness also was associated with higher absolute neutrophil to absolute lymphocyte (ANC/ALC) ratios in the entire sample at Day 30, which in turn was associated with Day 100 HRQOL. CONCLUSIONS: Findings demonstrate that pretransplant loneliness predicts HRQOL outcomes and associates with inflammatory immunological recovery patterns in HSCT patients. The balance of innate neutrophils to adaptive lymphocytes at Day 30 present a distinct profile in lonely individuals, with this immunity recovery profile predicting reduced HRQOL 100 days after the transplant. Addressing perceptions of loneliness before HSCT may be an important factor in improving immunological recovery and HRQOL outcomes.

Evaluation of Novel Targets, Including CC-Chemokine Receptor 4, in Adult T-Cell Acute Lymphoblastic Leukemia/Lymphoma: A Mayo Clinic Clinical and Pathologic Study.

CONTEXT.­: Unlike B-cell acute lymphoblastic leukemia/lymphoma (ALL/LBL), there have been few therapeutic advances in T-cell ALL (T-ALL)/LBL, an aggressive ALL/LBL subtype. OBJECTIVE.­: To perform a focused tissue array study to elucidate tumor markers of therapeutic potential in T-ALL/LBL. DESIGN.­: Using immunohistochemistry, we evaluated expression of leukemic antigens of interest, specifically CC-chemokine receptor 4 (CCR4), among others, on available remnant diagnostic material, including tumor tissue slides obtained from formalin-fixed, paraffin-embedded preserved tissues. RESULTS.­: Our analysis identified, for the first time, expression of CCR4 in T-ALL/LBL in 11 of 27 cases (40.7%) and confirmed common expression of BCL2, CD38, and CD47, as reported previously. We also identified the expression of CD123 in 4 of 26 cases (15.4%), whereas BCL6 and PDL1 were expressed in a small number of T-ALL/LBL cases. The potential novel target CCR4 was significantly more common in the Pre/Pro-T immunophenotypic subtype, 6 of 9 (66.7%, P = .01). No additional differences in clinical and epidemiologic variables were noted among positive or negative CCR4 cases. CONCLUSIONS.­: These findings support preclinical and clinical testing of therapies targeting CCR4, CD47, BCL2, CD38, and CD123 in T-ALL/LBL, and may help guide the development of targeted clinical trials in T-ALL/LBL, a rare disease in urgent need of novel therapies.

A clinical review of congenital hepatic fibrosis diagnosed in adulthood: presentation, complications, and outcomes.

INTRODUCTION AND OBJECTIVES: Congenital hepatic fibrosis (CHF) is a rare condition characterized by biliary tract changes and a geographic pattern of liver fibrosis. Liver biopsy is essential to confirm its diagnosis. The absence of specific clinical indicators in adults often leads to delays in diagnosis and management, while the natural history has not been well described. We sought to define the presentation and outcomes of adults with biopsy-proven CHF. MATERIALS AND METHODS: A retrospective chart review was conducted of patients diagnosed with CHF by liver biopsy. Continuous variables were summarized with the sample median and range. Categorical variables were summarized with number and percentage of patients. RESULTS: We identified 24 patients evaluated over a 20-year period, with a median age of 51 years (range 22-72 years) at initial presentation; 14 were male. The most common imaging findings were renal cysts (91.3%), splenomegaly (69.6%), and a cirrhotic-appearing liver (60.9%). The most commonly treated liver-related complications were cholangitis (45.8%), varices (45.8%), and hepatic encephalopathy (25%). Two patients died with a median length of follow-up of 2.9 years (range: 0.0-20.0 years). Two patients underwent transjugular intrahepatic portosystemic shunt (TIPS) placement to manage bleeding esophageal varices. Eight patients underwent liver transplantation (LT), the most common indication being decompensated disease (50%). CONCLUSIONS: CHF should be considered when patients present with cholangitis and/or complications of portal hypertension and have a cirrhotic appearing liver and renal cysts on imaging. Depending upon the disease severity, interventions such as TIPS or LT may be required.

Clinical and genetic predictors of cardiac dysfunction assessed by echocardiography in patients with hereditary hemochromatosis.

PURPOSE: Hereditary hemochromatosis (HH) may cause iron deposition in cardiac tissue. We aimed to describe the echocardiographic findings in patients with HH and identify risk factors for cardiac dysfunction. METHODS: In this retrospective study, we included patients with HH who underwent transthoracic echocardiography at our tertiary care center between August 2000 and July 2022. We defined three primary outcomes for cardiac dysfunction: 1) left ventricular ejection fraction (LVEF) < 55%, 2) ratio between early mitral inflow velocity and mitral annular early diastolic velocity (E/e') > 15, and 3) global longitudinal strain (GLS) < 18. Multivariable logistic regression was utilized to identify predictors of cardiac dysfunction. RESULTS: 582 patients (median age 57 years, 61.2% male) were included. The frequency of LVEF < 55%, E/e' > 15 and GLS < 18 was 9.0% (52/580), 9.6% (51/534) and 20.2% (25/124), respectively. In multivariable analysis, non-White race, age, and hypertension were associated with E/e' > 15. No specific HFE genetic mutation was associated with LVEF < 55%. A history of myocardial infarction was strongly associated with both LVEF < 55% and E/e' > 15. In patients with LVEF ≥ 55%, the C282Y/H63D genetic mutation was associated with reduced likelihood of E/e' > 15, p = 0.024. Patients with C282Y/H63D had a higher frequency of myocardial infarction. Smoking and alcohol use were significantly associated with GLS < 18 in unadjusted analysis. CONCLUSION: We found the traditional risk factors of male sex, and history of myocardial infarction or heart failure, were associated with a reduced LVEF, irrespective of the underlying HFE genetic mutation. Patients with a C282Y/H63D genetic mutation had a higher frequency of myocardial infarction, yet this mutation was associated with reduced odds of diastolic dysfunction compared to other genetic mutations in patients with a normal LVEF.

Skin Cancer in Non-White Solid Organ Transplant Recipients: Mayo Clinic Experience.

OBJECTIVE: Solid organ transplant recipients (SOTRs) have an increased risk of skin cancer development, but limited data exist on the development pattern of cutaneous malignancies in non-White SOTRs. The aim of this study was to describe the characteristics and outcomes of non-White patients who developed skin cancer following solid organ transplantation. METHODS: We conducted a retrospective chart review of non-White SOTRs at the Mayo Clinic who underwent transplantation between November 1987 and April 2020 and subsequently developed skin cancer. RESULTS: We identified 32 non-White SOTRs who developed skin cancer in the posttransplant period. Among these, 46.9% were Hispanic/Latinx, 25% were American Indian/Alaskan Native, 21.9% were Asian, and 6.3% were Black/African American. Four patients had a history of nonmelanoma skin cancer pretransplant. In regard to skin cancer type, 21 (65.6%) patients developed squamous cell carcinoma, 15 (46.9%) developed basal cell carcinoma, 5 (15.6%) developed melanoma, and 2 (6.3%) developed sebaceous carcinoma. The median time from transplant to first posttransplant skin cancer was 7.8 years. CONCLUSIONS: Our study provides further characterization of the development of skin cancer in non-White SOTRs following transplant and identifies a variety of relevant pre- and posttransplant factors. Despite a long follow-up period, the number of patients identified remained low, which is consistent with the literature, indicating a low incidence of skin cancer development in non-White SOTRs. Continued investigation may allow for a more precise identification of risk factors and their degree of significance.

A Pilot, Randomized, Single-Blind, Controlled Study Evaluating the Use of Platelet Rich Plasma (PRP) for Hand Skin Rejuvenation.

BACKGROUND: The presence of various growth factors in platelets makes platelet rich plasma a powerful tool in the stimulation of collagen regeneration in aging skin. The main objective of this study was to determine efficacy and safety of platelet rich plasma compared to saline solution in women with aging skin of the hands. METHODS: In this prospective, randomized clinical trial, eighteen women with hand aging received PRP injections every 4 weeks into the unilateral dorsal hand for 12 weeks total; with saline injections into the contralateral hand in a randomized, controlled, single-blind fashion. Physician assessment, photographs and quality-of-life questionnaires were used for assessment at baseline; 12- and 24-week follow-up. RESULTS: The majority of patients reported pain and discomfort along with a burning/stinging sensation in both PRP and saline treated hands with no significant differences noted in any patient outcome measures between the two treatments (all P≥0.25). No differences were reliably detected between the treatment hands by a blinded investigator comparing before and after clinical photographs of the hands. CONCLUSION: Three injections of PRP spaced 4 weeks apart did not appear to be effective for treatment of aging skin of the hands in women, with no noted difference as compared with baseline, or saline injection. Although age > 45 years may be a factor accounting for non-response (i.e., subtle skin changes are difficult to appreciate, and possible limited platelet regenerative capacity in advanced age) it appears that PRP is not a reliable cosmetic option for management of hand aging.

Metabolic liver cancer: associations of rare and common germline variants in one-carbon metabolism and DNA methylation genes.

Animal studies implicate one-carbon metabolism and DNA methylation genes in hepatocellular carcinoma (HCC) development in the setting of metabolic perturbations. Using human samples, we investigated the associations between common and rare variants in these closely related biochemical pathways and risk for metabolic HCC development in a multicenter international study. We performed targeted exome sequencing of 64 genes among 556 metabolic HCC cases and 643 cancer-free controls with metabolic conditions. Multivariable logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for multiple comparisons. Gene-burden tests were used for rare variant associations. Analyses were performed in the overall sample and among non-Hispanic whites. The results show that among non-Hispanic whites, presence of rare functional variants in ABCC2 was associated with 7-fold higher risk of metabolic HCC (OR = 6.92, 95% CI: 2.38-20.15, P = 0.0004), and this association remained significant when analyses were restricted to functional rare variants observed in ≥2 participants (cases 3.2% versus controls 0.0%, P = 1.02 × 10-5). In the overall multiethnic sample, presence of rare functional variants in ABCC2 was nominally associated with metabolic HCC (OR = 3.60, 95% CI: 1.52-8.58, P = 0.004), with similar nominal association when analyses were restricted to functional rare variants observed in ≥2 participants (cases 2.9% versus controls 0.2%, P = 0.006). A common variant in PNPLA3 (rs738409[G]) was associated with higher HCC risk in the overall sample (P = 6.36 × 10-6) and in non-Hispanic whites (P = 0.0002). Our findings indicate that rare functional variants in ABCC2 are associated with susceptibility to metabolic HCC in non-Hispanic whites. PNPLA3-rs738409 is also associated with metabolic HCC risk.

Surgical service and distance traveled drive patient preference for Care Hotel: a retrospective cohort study.

Mayo Clinic's Care Hotel is a virtual hybrid care model which allows postoperative patients to recover in a comfortable environment after a low-risk procedure. Hospitals need to understand the key patient factors that promote acceptance of the Care Hotel if they are to benefit from this innovative care model. This study aims to identify factors that can predict whether a patient will stay at Care Hotel. Materials and methods: This retrospective chart review of 1065 patients was conducted between 23 July 2020, and 31 December 2021. Variables examined included patient age, sex, race, ethnicity, Charlson comorbidity index, distance patient travelled to hospital, length of surgery, day of the week of surgery, and surgical service. Associations of patient and surgery characteristics with the primary outcome of staying at the Care Hotel were assessed using unadjusted and multivariable logistic regression models. Results: Of the 1065 patients who met criteria for admission to the Care Hotel during the study period, 717 (67.3%) chose to stay at the Care Hotel while 328 (32.7%) choose to be admitted to the hospital. In multivariable analysis, there was a significant association between surgical service and staying at the Care Hotel (P<0.001). Specifically, there was a higher likelihood of staying at the Care Hotel for patients from Neurosurgery [odds rato (OR)=1.86, P=0.004], Otorhinolaryngology (OR=2.70, P<0.001), and General Surgery (OR=2.75, P=0.002). Additionally, there was a higher likelihood of staying at the Care Hotel with distance travelled over 110 miles [OR (per each doubling)=1.10, P=0.007]. Conclusion: When developing a post-surgical care model for patients following outpatient procedures, the referring surgical service is a primary factor to consider in order to ensure patient acceptance, along with patient distance. This study can assist other healthcare organizations considering this model, as it provides guidance on which factors are most indicative of acceptance.

Use of prophylactic ureteral stents in gynecologic surgery.

BACKGROUND: The aim of this study was to evaluate rate of complications with the use of prophylactic ureteral localization stents (PULSe) in gynecologic surgery. To compare the occurrence of complications according to the indication of surgery. METHODS: This retrospective study included 1248 women who underwent 1275 different gynecologic surgeries with PULSe between 2007 and 2020. Data was collected regarding patient characteristics (age, sex, race, ethnicity, parity, previous pelvic surgery, creatinine), operative characteristics (trainee, guidewire use, indication) and complications in the first 30 days (ureteral injury, urinary tract complication, re-stenting, hydronephrosis, urinary tract infection (UTI), pyelonephritis, emergency room visit, re-admission). RESULTS: Median age was 57 years (range: 18-96 years), most women were Caucasian (88.9%), and had previous pelvic surgery (77.7%). Indication of surgery was benign for 459 (36.0%), female pelvic medicine and reconstructive surgery (FPMRS) for 545 (42.7%), and gynecologic oncology (gyn-onc) for 271 (21.3%). Disabling complications occurred rarely with 8 patients (0.6%) having a ≥III Clavien Dindo Grade (CDG), and only 1 (0.08%) ≥IV CDG. Statistically significant differences between benign, FPMRS, and gyn-onc groups were noted for re-stenting (0.9% vs. 0.0% vs. 1.1%, P=0.020), hydronephrosis (0.9% vs. 0.2% vs. 2.2%, P=0.014), UTI (4.6% vs. 9.4% vs. 7.0%, P=0.016), and re-admission (2.4% vs. 1.1% vs. 4.4%, P=0.014). CONCLUSIONS: The incidence of 30-day CDG III and IV complications after PULSe placement is low. FPMRS patients had a higher rate of complicated UTI, however gyn- onc patients appear to be at overall higher risk of stent related complications when compared to surgeries for FPMRS or benign indications.

Comparison of onset of neuromuscular blockade with electromyographic and acceleromyographic monitoring: a prospective clinical trial.

BACKGROUND: Reliable devices that quantitatively monitor the level of neuromuscular blockade after neuromuscular blocking agents' administration are crucial. Electromyography and acceleromyography are two monitoring modalities commonly used in clinical practice. The primary outcome of this study is to compare the onset of neuromuscular blockade, defined as a Train-Of-Four Count (TOFC) equal to 0, as measured by an electromyography-based device (TetraGraph) and an acceleromyography-based device (TOFscan). The secondary outcome was to compare intubating conditions when one of these two devices reached a TOFC equal to 0. METHODS: One hundred adult patients scheduled for elective surgery requiring neuromuscular blockade were enrolled. Prior to induction of anesthesia, TetraGraph electrodes were placed over the forearm of patients' dominant/non-dominant hand based on randomization and TOFscan electrodes placed on the contralateral forearm. Intraoperative neuromuscular blocking agent dose was standardized to 0.5 mg.kg-1 of rocuronium. After baseline values were obtained, objective measurements were recorded every 20 seconds and intubation was performed using video laryngoscopy once either device displayed a TOFC = 0. The anesthesia provider was then surveyed about intubating conditions. RESULTS: Baseline TetraGraph train-of-four ratios were higher than those obtained with TOFscan (Median: 1.02 [0.88, 1.20] vs. 1.00 [0.64, 1.01], respectively, p < 0.001). The time to reach a TOFC = 0 was significantly longer when measured with TetraGraph compared to TOFscan (Median: 160 [40, 900] vs. 120 [60, 300] seconds, respectively, p < 0.001). There was no significant difference in intubating conditions when either device was used to determine the timing of endotracheal intubation. CONCLUSIONS: The onset of neuromuscular blockade was longer when measured with TetraGraph than TOFscan, and a train-of-four count of zero in either device was a useful indicator for adequate intubating conditions. CLINICAL TRIAL NUMBER AND REGISTRY: URL NCT05120999, https://clinicaltrials.gov/ct2/show/NCT05120999.

Comparison of Migraine Characteristics in Patients With and Without Inflammatory Bowel Disease: A Retrospective Cohort Study.

BACKGROUND: Survey studies have found an increased prevalence of migraine in patients with inflammatory bowel disease (IBD). However, the clinical characteristics of migraines in this population are unknown. We conducted a retrospective medical record review study to characterize migraines in the IBD population. METHODS: Six hundred seventy-five migraine patients (280 with IBD, 395 without IBD) who were evaluated at Mayo Clinic Rochester, Mayo Clinic Arizona, or Mayo Clinic Florida between July 2009 and March 2021 were included. Patients with ICD codes for migraine and either Crohn's disease (CD) or ulcerative colitis (UC) were selected. Electronic health care records were reviewed. Patients confirmed to have IBD and migraine were included. Demographic, IBD, and migraine characteristics were collected. Statistical analysis was completed using SAS. RESULTS: Patients with IBD were less often male (8.6% vs 21.3%, P < .001) and had a higher Charlson Comorbidity Index (>2: 24.6% vs 15.7%, P = .003); 54.6% had CD and 39.3% had UC. Patients with IBD had migraine with aura and without aura more frequently ( OR 2.20, P < .001 and OR 2.79, P < .001, respectively) than non-IBD patients. Additionally, those with IBD less commonly had chronic migraine (OR 0.23, P < .001) and less commonly had chronic migraine or treatment for migraine (ORs 0.23-0.55, P ≤ .002). CONCLUSIONS: Migraine with and without aura have increased prevalence in IBD patients. Further study of this topic will be helpful to clarify the prevalence of migraine, establish this population's response to treatment, and better understand the reason(s) for a low rate of treatment.

A Parathyroid Hormone-Guided Calcium and Calcitriol Supplementation Protocol Reduces Hypocalcemia-Related Readmissions Following Total Thyroidectomy.

OBJECTIVE: To determine the effect of a 4-hour postoperative serum parathyroid hormone (PTH)-guided calcium (Ca) and calcitriol supplementation protocol on the incidence of hypocalcemia and hospital readmissions in patients undergoing total thyroidectomy. METHODS: This was a single-institution, retrospective chart review of patients who underwent total thyroidectomy; 148 and 389 of the patients underwent surgery prior to and after the protocol implementation, respectively. The risk of hypocalcemia was stratified as low (PTH level of >30 pg/mL), medium (15-30 pg/mL), and high (<15 pg/mL), using serum PTH values obtained 4 hours postoperatively. Hypocalcemia was defined as a total serum Ca level of <8 mg/dL. Baseline demographic and operative characteristics and postoperative outcome were recorded for both groups. The Fisher exact test and Wilcoxon rank sum test were used to compare the characteristics of the 2 groups. A multivariate logistic regression model was applied to account for potentially confounding variables. RESULTS: Postoperative hypocalcemia occurred significantly less frequently in the protocol group compared with that in the preprotocol group (10.3% vs 20.9%, P = .002). The reduction in hypocalcemia in the protocol group was observed in both patients with (16.3% vs 25.6%) and without (8.4% vs 19.3%) cervical lymph node dissection. The protocol group had a significantly lower incidence of hospital readmission events than the preprotocol group (1.0% vs 4.7%, P = .013). CONCLUSION: Compared with a historical cohort, a PTH-guided protocol for Ca and calcitriol supplementation significantly reduces the postoperative hypocalcemia and hospital readmission rates in patients undergoing total thyroidectomy.

A Pilot Study of Intralesional Injection of Triamcinolone Acetonide for Desmoid Tumors: Two-Year Outcomes.

PURPOSE: The purpose of this pilot study was to examine the clinical efficacy and safety of serial triamcinolone injections for the treatment of desmoid tumors. PATIENTS AND METHODS: Nine patients were enrolled into this prospective study and underwent three serial ultrasound-guided triamcinolone injections (120 mg) at 6-week intervals. MRI was compared at baseline and every 6 months, out to 24 months. Safety and tolerability were assessed by clinical evaluation and questionnaires, including the 12-item short form survey (SF-12), visual analog scale (VAS), and desmoid patient-reported outcome (PRO) tool. RESULTS: At 24 months, 8 (88.9%) patients demonstrated a reduction in the volume of their tumor while 1 (11.1%) enlarged. Median tumor volume change was -26.9% (-81.1% to 34.6%; P = 0.055) All 9 tumors remained stable based on World Health Organization criteria, whereas 2 (22.2%) demonstrated partial response based on RECIST. There was a significant decrease in the tumor:muscle postcontrast mean signal intensity ratio at 6 months (P = 0.008) and 24 months (P = 0.004). There was a similar decrease in the tumor:muscle T2 mean signal intensity ratio at 24 months (P = 0.02). We found no difference in the SF-12 and VAS scores, but there were significant improvements in the desmoid PRO. CONCLUSIONS: Treatment of desmoid tumors with serial triamcinolone injections appears safe and well tolerated by patients, with a 22% partial response based on RECIST. Further research is needed to confirm our results and determine factors predictive of response.

Comparison of onset of neuromuscular blockade with electromyographic and acceleromyographic monitoring: a prospective clinical trial

Abstract Background Reliable devices that quantitatively monitor the level of neuromuscular blockade after neuromuscular blocking agents' administration are crucial. Electromyography and acceleromyography are two monitoring modalities commonly used in clinical practice. The primary outcome of this study is to compare the onset of neuromuscular blockade, defined as a Train-Of-Four Count (TOFC) equal to 0, as measured by an electromyography-based device (TetraGraph) and an acceleromyography-based device (TOFscan). The secondary outcome was to compare intubating conditions when one of these two devices reached a TOFC equal to 0. Methods One hundred adult patients scheduled for elective surgery requiring neuromuscular blockade were enrolled. Prior to induction of anesthesia, TetraGraph electrodes were placed over the forearm of patients' dominant/non-dominant hand based on randomization and TOFscan electrodes placed on the contralateral forearm. Intraoperative neuromuscular blocking agent dose was standardized to 0.5 mg.kg−1 of rocuronium. After baseline values were obtained, objective measurements were recorded every 20 seconds and intubation was performed using video laryngoscopy once either device displayed a TOFC = 0. The anesthesia provider was then surveyed about intubating conditions. Results Baseline TetraGraph train-of-four ratios were higher than those obtained with TOFscan (Median: 1.02 [0.88, 1.20] vs. 1.00 [0.64, 1.01], respectively, p < 0.001). The time to reach a TOFC = 0 was significantly longer when measured with TetraGraph compared to TOFscan (Median: 160 [40, 900] vs. 120 [60, 300] seconds, respectively, p < 0.001). There was no significant difference in intubating conditions when either device was used to determine the timing of endotracheal intubation. Conclusions The onset of neuromuscular blockade was longer when measured with TetraGraph than TOFscan, and a train-of-four count of zero in either device was a useful indicator for adequate intubating conditions. Clinical trial number and registry URL NCT05120999, https://clinicaltrials.gov/ct2/show/NCT05120999.

Hematopoietic Stem Cell Transplantation in CSF1R-Related Leukoencephalopathy: Retrospective Study on Predictors of Outcomes.

Mutations in the CSF1R gene are the most common cause of adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a neurodegenerative disease with rapid progression and ominous prognosis. Hematopoietic stem cell transplantation (HSCT) has been increasingly offered to patients with CSF1R-ALSP. However, different therapy results were observed, and it was not elucidated which patient should be referred for HSCT. This study aimed to determine predictors of good and bad HSCT outcomes in CSF1R-ALSP. We retrospectively analyzed 15 patients, 14 symptomatic and 1 asymptomatic, with CSF1R-ALSP that underwent HSCT. Median age of onset was 39 years, and the median age of HSCT was 43 years. Cognitive impairment was the most frequent initial manifestation (43%), followed by gait problems (21%) and neuropsychiatric symptoms (21%). Median post-HSCT follow-up was 26 months. Good outcomes were associated with gait problems as initial (p = 0.041) and predominant (p = 0.017) manifestation and younger age at HSCT (p = 0.044). Cognitive impairment as first manifestation was a predictor of a bad outcome (p = 0.016) and worsening of cognition post-HSCT (p = 0.025). In conclusion, gait problems indicated a milder phenotype with better response to HSCT and good therapy outcomes. In contrast, patients with a higher burden of cognitive symptoms were most likely not to benefit from HSCT.

A retrospective case series of prophylactic neurectomy during total knee arthroplasty.

INTRODUCTION: Total knee arthroplasty is a common operation performed to relieve pain and restore functional activity. While overall widely successful, a subset of patients has continued pain postoperatively with no identifiable cause. Neuroma formation has been identified as a possible contributor to this unexplained pain, often necessitating an additional procedure for neuroma removal. The purpose of our study was to evaluate if prophylactic neurectomy could reduce the occurrence of postoperative pain. METHODS: A total of 112 patients were compared, 44 control patients and 68 neurectomy patients. Demographic information, Numerical rating pain scale (NRS) and Knee Society Scores (KSS) were collected pre- and post-operatively. Patients were additional asked if they were overall satisfied with the operation. RESULTS: There were no differences between groups with respect to age (Median: 71 vs 69 years, p = 0.28), male sex (41% vs 44%, p = 0.85), or body mass index (Median: 32.2 vs 31.3, p = 0.80). When comparing the degree of change following surgery there were no statistically significant differences observed in NRS pain scores (Median change: -7 vs -6, p = 0.89) or KSS scores (Median change: +44 vs +40, p = 0.14). Similarly, there was no statistically significant difference in overall patient-reported satisfaction with the knee replacement (82.5% vs 86.6%, p = 0.59). CONCLUSION: We did not find a statistically significant difference in NRS, KSS, or overall patient satisfaction between the prophylactic neurectomy and control patient groups. Larger studies with evaluation of the nerve diameter will be needed to determine which patients are at risk for symptomatic neuroma development following total knee arthroplasty.