The Use of Semaglutide in Patients With Renal Failure-A Retrospective Cohort Study.

OBJECTIVE: Semaglutide, a glucagon-like peptide-1 receptor agonist is approved for weight loss and diabetes treatment, but limited literature exists regarding semaglutide use in patients with advanced chronic kidney disease (CKD). Therefore, this project assessed the safety and efficacy of semaglutide among patients with estimated glomerular filtration rate (eGFR) 15-29 mL/min/1.73 m2 (CKD stage 4), eGFR<15 mL/min/1.73 m2 (CKD stage 5) or on dialysis. METHODS: This is a retrospective electronic medical record based analysis of consecutive patients with advanced CKD (defined as CKD 4 or greater) who were started on semaglutide (injectable or oral). Data was collected between January 2018 and January 2023. Investigators verified CKD diagnosis and manually extracted data. Data were analyzed using Fisher's exact test, paired t test, linear mixed effects models and Wilcoxon signed rank test. RESULTS: Seventy-six patients with CKD 4 or greater who initiated semaglutide were included. Most patients had a history of type 2 diabetes mellitus (96.0%), and most were males (53.9%). The mean age was 66.8 y (SD 11.5) with the mean body mass index was 36.2 (SD 7.5). The initial doses were 3 mg orally and 0.25 mg by injection. Maximum prescribed dose was 1 mg (injectable) in 28 (45.2%) patients and 14 mg (orally) in 2 (14.2%) patients. Patients received semaglutide for a median duration of 17.4 (IQR 0.43, 48.8) months. Forty-eight (63.1%) patients reported no adverse effects associated with the therapy. Mean weight decreased from 106.2 (SD 24.2) to 101.3 (SD 27.3) kg (P < .001). Eight patients (16%) with type 2 diabetes mellitus T2DM discontinued insulin after starting semaglutide. Mean hemoglobin A1c (HbA1c) decreased from 8.0% (SD 1.7) to 7.1% (SD 1.3) (P < .001). Adverse effects were the primary reason for semaglutide discontinuation (37.0%), with nausea, vomiting, and abdominal pain being the most common complaints. CONCLUSIONS: Based on this retrospective study semaglutide appears to be tolerated by most individuals with CKD 4 or greater despite associated gastrointestinal side effects similar to those observed in patients with better kidney function and leads to an improvement of glycemic control and insulin discontinuation in patients with T2DM. Modest weight loss (approximately 4.6% of the total body weight) was observed on the prescribed doses. Larger prospective randomized studies are needed to comprehensively assess the risks and benefits of semaglutide in patients with CKD 4 or greater and obesity.

Risk factors and outcomes of Pneumocystis pneumonia in solid organ transplant recipients: Impact of posttransplant lymphoproliferative disorder.

BACKGROUND: Pneumocystis jirovecii pneumonia (PJP) is a potentially fatal infection afflicting the immunocompromised population, including solid organ transplant (SOT) recipients. Several risk factors have been described; however, little is known regarding the risk of PJP in SOT recipients with posttransplant lymphoproliferative disorder (PTLD). METHODS: We performed a nested case-control study of SOT recipients diagnosed with PJP from 2000 to 2020. PJP was defined as positive microscopy or polymerase chain reaction testing with compatible symptoms and radiographic findings. Control patients were matched 2:1 by year of first transplant, first transplanted organ, transplant center, and sex. Multivariable conditional logistic regression was performed to test associations with PJP and Cox regression analyzed post-PJP outcomes. RESULTS: Sixty-seven PJP cases were matched to 134 controls. The most common transplant was kidney (55.2%). Fourteen patients had a history of PTLD, 12 of whom developed PJP. After adjusting for age, acute rejection, cytomegalovirus infection, PJP prophylaxis, and lymphopenia (lymphocyte count < .5 × 109 /L), PTLD was independently associated with PJP (OR 14.0, 95% CI 1.7-114.5; p = .014). Lymphopenia was also a significant association (OR 8.2, 95% CI 3.2-20.7; p < .001). PJP was associated with mortality within 90 days of diagnosis (p < .001), but not after 90 days (p = .317). PJP was also associated with 90-day death-censored renal allograft loss (p = .026). CONCLUSIONS: PTLD is independently associated with PJP after adjustment for recognized risk factors. This is likely influenced by PTLD-directed chemotherapy, particularly rituximab-containing regimens. PJP is associated with early mortality, but this effect is not persistent after 90 days. PJP prophylaxis should be considered in SOT recipients with PTLD.

Risk factors and prophylaxis for nocardiosis in solid organ transplant recipients: A nested case-control study.

BACKGROUND: Nocardia is an opportunistic pathogen that primarily affects immunocompromised individuals, including solid organ transplant (SOT) recipients. Up to 2.65% of SOT recipients develop nocardiosis; however, few studies have examined risk factors and prophylaxis for nocardiosis. METHODS: We performed a multicenter, matched nested case-control study of adult SOT recipients with culture-confirmed nocardiosis from 2000 through 2020. Controls were matched up to 2:1 by sex, first transplanted organ, year of transplant, transplant center, and adequate post-transplant follow-up. Multivariable conditional logistic regression was performed to analyze associations with nocardiosis. Cox proportional hazards regression compared 12-month mortality between infection and uninfected patients. RESULTS: One hundred and twenty-three SOT recipients were matched to 245 uninfected controls. Elevated calcineurin inhibitor level, acute rejection, cytomegalovirus infection, lymphopenia, higher prednisone dose, and older age were significantly associated with nocardiosis while trimethoprim-sulfamethoxazole prophylaxis was protective (odds ratio [OR] .34; 95% confidence interval [CI] .13-.84). The effect of prophylaxis was similar, though not always statistically significant, in sensitivity analyses that only included prophylaxis dosed more than twice-per-week (OR .30; 95% CI .11-.80) or restricted to years 2015-2020 (OR .33, 95% CI .09-1.21). Nocardiosis was associated with increased 12-month mortality (hazard ratio 5.47; 95% confidence interval 2.42-12.35). CONCLUSIONS: Multiple measures of immunosuppression and lack of trimethoprim-sulfamethoxazole prophylaxis were associated with nocardiosis in SOT recipients. Effectiveness of prophylaxis may be related to trimethoprim-sulfamethoxazole dose or frequency. Trimethoprim-sulfamethoxazole should be preferentially utilized over alternative agents in SOT recipients with augmented immunosuppression or signs of heightened immunocompromise.

Weight Loss Surgery Increases Kidney Transplant Rates in Patients With Renal Failure and Obesity.

OBJECTIVE: To describe the outcomes of kidney transplant (KT) candidates with obesity undergoing sleeve gastrectomy (SG) to meet the criteria for KT. METHODS: Retrospective analysis was conducted of electronic medical records of KT candidates with obesity (body mass index >35 kg/m2) who underwent SG in our institution. Weight loss, adverse health events, and the listing and transplant rates were abstracted and compared with the nonsurgical cohort. RESULTS: The SG was performed in 54 patients; 50 patients did not have surgery. Baseline demographic characteristics were comparable at the time of evaluation. Mean body mass index ± SD of the SG group was 41.7±3.6 kg/m2 at baseline (vs 41.5±4.3 kg/m2 for nonsurgical controls); at 2 and 12 months after SG, it was 36.4±4.1 kg/m2 and 32.6±4.0 kg/m2 (P<.01 for both). In the median follow-up time of 15.5 months (interquartile range, 6.4 to 23.9 months), SG was followed by active listing (37/54 people), and 20 of 54 received KT during a median follow-up time of 20.9 months (interquartile range, 14.7 to 28.3 months) after SG. In contrast, 14 of 50 patients in the nonsurgical cohort were listed, and 5 received a KT (P<.01). Three patients (5.6%) experienced surgical complications. There was no difference in overall hospitalization rates and adverse health outcomes, but the SG cohort experienced a higher risk of clinically significant functional decline. CONCLUSION: In KT candidates with obesity, SG appears to be effective, with 37% of patients undergoing KT during the next 18 months (P<.01). Further research is needed to confirm and to improve the safety and efficacy of SG for patients with obesity seeking a KT.

Laboratory evaluation for the differential diagnosis of possible multiple sclerosis in the United States: A physician survey.

BACKGROUND: There is limited evidence and lack of guidelines for diagnostic laboratory evaluation of patients with possible multiple sclerosis (MS). OBJECTIVE: To survey neurologists on their practice of laboratory testing in patients with possible MS. METHODS: An online survey was developed to query the frequency of serum and cerebrospinal fluid (CSF) studies ordered in the routine evaluation of patients with possible MS, and in three hypothetical clinical cases. Non-MS specialist neurologists who evaluate patients for MS in their practice were invited to participate by MedSurvey (a medical market research company). RESULTS: The survey was completed by 190 neurologists. A mean of 17.2 (SD: 17.0) tests in serum and CSF were reported "always" ordered in the evaluation of patients with possible MS. CSF oligoclonal bands was the most frequently selected ("always" among 73.7% of participants). Antinuclear antibody (43.2%), erythrocyte sedimentation rate (34.2%), and thyroid stimulating hormone (31.6%) were also among the most frequently ordered. DISCUSSION: Extensive laboratory evaluations are often completed in the evaluation of possible MS. However, many of these tests have poor specificity and false positive results could yield unnecessary increased costs, diagnostic delay, and potentially misdiagnosis. Further research is needed to identify optimal laboratory approaches for possible MS.

Pericardial Effusion as a Purported Manifestation of Graft-versus-Host Disease following Allogeneic Hematopoietic Cell Transplantation.

Large pericardial effusion (LPE) and tamponade are purported manifestations associated with atypical chronic graft-versus-host disease (cGVHD); however, their temporal association with GVHD, management, and impact on overall outcome are not well established. We report a retrospective analysis of 38 patients who developed LPE from a cohort of 1265 (3.00%) patients age ≥18 years who underwent allogeneic hematopoietic cell transplantation (alloHCT) at Mayo Clinic between March 1993 and August 2020. The median patient age at the time of LPE was 54 years (interquartile range [IQR], 44 to 58 years), and 8 of the 38 patients (21%) had previous cardiomyopathy. The median time from alloHCT to detection of LPE was 197 days (IQR, 40 to 378 days). Overall, the incidence of grade II (15 of 38; 40%) and grade III-IV (9 of 38; 24%) acute GVHD (aGVHD) was higher in patients who developed LPE compared with those who did not develop LPE (P = .005). The incidence rates of moderate (10 of 38; 26%) and severe (15 of 38; 40%) cGVHD according to the 2014 National Institutes of Health cGVHD criteria were also higher in the LPE cohort (P = .03). Twenty-nine patients (76%) presented with cardiac tamponade, 32 patients (84%) underwent urgent pericardiocentesis for symptomatic LPE, and 2 patients had a pericardial window placement. Four patients were medically managed with colchicine, steroids, diuresis, and immunosuppressive therapy (IST). On multivariable analysis, HCT Comorbidity Index (HCT-CI) group (hazard ratio [HR] 3.57; [95% confidence interval (CI), 1.29 to 9.85; P = .014] for HCT-CI 1 to 2; 4.06 [95% CI, 1.50 to 10.99; P = .006] for HCT-CI ≥3) and aGVHD (HR, 2.38 [95% CI, 1.11 to 5.12; P = .026] for grade II and 2.82 [95% CI, 1.07 to 7.44; P = .038] for grade III-IV) were significant risk factors for developing LPE. At a median follow-up of 40 months post-alloHCT, median disease-free survival (DFS) was 34.2 months (95% CI, 25.3 to 45.7 months) in patients who did not develop LPE and 32.2 months (95% CI, 13.2 to undefined upper limit) in those who developed LPE (P = .41). The median overall survival (OS) post-alloHCT was 50.9 months (95% CI, 41.8 to 64.8 months) in patients who did not develop LPE and was 32.9 months (95% CI, 19.5 to undefined upper limit) in patients who developed LPE (P = .003). In summary, LPE and tamponade can present at various time points post-alloHCT, and management includes pericardiocentesis, steroids, and intensification/initiation of IST if associated with serositis. LPE does not appear to result in permanent cardiac damage but results in inferior OS.

ADC restriction is not associated with clinical response to plasma exchange following a cerebral attack of multiple sclerosis.

BACKGROUND: MS is the most common CNS inflammatory demyelinating disease. Plasma exchange (PLEX) has well-demonstrated efficacy in acute corticosteroid-refractory attacks of demyelination but identifying the factors that predict favorable PLEX response remains elusive. We aimed to determine if apparent diffusion coefficient (ADC) restriction on brain MRI predicts clinical response to PLEX in individuals with an acute cerebral attack of MS. METHODS: Retrospective chart review of individuals with a cerebral attack of MS who underwent PLEX at Mayo Clinic. RESULTS: We identified 34 individuals who fulfilled the inclusion criteria. Twenty-seven (79%) responded to plasma exchange, with 16/34 (47%) having moderate and 11/34 (32%) marked improvement. Twenty-three (68%) people had ADC restriction on brain MRI prior to PLEX.  ADC restriction did not predict response (p = 0.51). Several other pre-PLEX factors, including sex, Expanded Disability Status Scale (EDSS) at initial attack, time to PLEX, and concurrent spinal cord attack, also failed to predict response. Plasma-exchange responders had less disability at 6-month follow-up compared to non-responders (median EDSS 2.5 (range 1.0-10.0) vs. 7.5 (5.5-10.0), p<0.001). CONCLUSION: Acute cerebral attacks of MS have a high rate of plasma exchange response resulting in a lower EDSS at 6-months. ADC restriction does not predict response to plasma exchange.

Stiff person spectrum disorder diagnosis, misdiagnosis, and suggested diagnostic criteria.

BACKGROUND: Stiff person spectrum disorder (SPSD) is heterogeneous, and accurate diagnosis can be challenging. METHODS: Patients referred for diagnosis/suspicion of SPSD at the Mayo Autoimmune Neurology Clinic from July 01, 2016, to June 30, 2021, were retrospectively identified. SPSD diagnosis was defined as clinical SPSD manifestations confirmed by an autoimmune neurologist and seropositivity for high-titer GAD65-IgG (>20.0 nmol/L), glycine-receptor-IgG or amphiphysin-IgG, and/or confirmatory electrodiagnostic studies (essential if seronegative). Clinical presentation, examination, and ancillary testing were compared to differentiate SPSD from non-SPSD. RESULTS: Of 173 cases, 48 (28%) were diagnosed with SPSD and 125 (72%) with non-SPSD. Most SPSD were seropositive (41/48: GAD65-IgG 28/41, glycine-receptor-IgG 12/41, amphiphysin-IgG 2/41). Pain syndromes or functional neurologic disorder were the most common non-SPSD diagnoses (81/125, 65%). SPSD patients more commonly reported exaggerated startle (81% vs. 56%, p = 0.02), unexplained falls (76% vs. 46%, p = 0.001), and other associated autoimmunity (50% vs. 27%, p = 0.005). SPSD more often had hypertonia (60% vs. 24%, p < 0.001), hyperreflexia (71% vs. 43%, p = 0.001), and lumbar hyperlordosis (67% vs. 9%, p < 0.001) and less likely functional neurologic signs (6% vs. 33%, p = 0.001). SPSD patients more frequently had electrodiagnostic abnormalities (74% vs. 17%, p < 0.001), and at least moderate symptomatic improvement with benzodiazepines (51% vs. 16%, p < 0.001) or immunotherapy (45% vs. 13% p < 0.001). Only 4/78 non-SPSD patients who received immunotherapy had alternative neurologic autoimmunity. INTERPRETATION: Misdiagnosis was threefold more common than confirmed SPSD. Functional or non-neurologic disorders accounted for most misdiagnoses. Clinical and ancillary testing factors can reduce misdiagnosis and exposure to unnecessary treatments. SPSD diagnostic criteria are suggested.