Outcomes of Percutaneous Endoscopic Gastrostomy in Huntington's Disease at a Tertiary Center.

BACKGROUND: Clinically assisted nutrition and hydration via percutaneous endoscopic gastrostomy (PEG) is a therapeutic option to ameliorate the difficulties associated with enhanced catabolism, weight loss, and dysphagia in Huntington's disease (HD). OBJECTIVES: The objective is to provide insights into demographics, staging (Shoulson-Fahn), complications, weight trajectories, and survival rates in people with HD (pwHD) who underwent PEG. METHODS: This retrospective study included 705 consecutive pwHD who attended our HD clinic between July 2006 and March 2024, of whom 52 underwent PEG. A control group (n = 52), comprising pwHD without PEG, were closely matched for sex, stage, age, CAG length, and disease burden score at PEG. The study was registered as a service evaluation at the National Hospital for Neurology and Neurosurgery. RESULTS: PEG prevalence was 15.0% (n = 52/347) among manifest pwHD: 4.8% (n = 3/62) for Stage 3; 33.3% (n = 16/48) for stage 4; and 44.1% (n = 30/68) for stage 5. Commonest indications were dysphagia, weight loss, and inadequate oral intake. Complications included chest infection, tube dislodgement, and peristomal and skin infections. Modeling of weight trajectories after PEG found no difference between PEG and non-PEG groups. Mortality rate was 34.6% (n = 18/52) in the PEG and 36.5% (n = 19/52) in the non-PEG groups (P = 0.84). Treatment duration (until study endpoint or death) was 3.48 years (interquartile range = 1.71-6.02; range = 0.23-18.8), with 65.4% (n = 34/52) alive at the study endpoint. CONCLUSION: PEG in pwHD at-risk for weight loss may help slow weight loss. Prospective studies are required to strengthen PEG decision-making in pwHD. PEG survival was much longer than other dementias, highlighting the need to consider PEG independently in pwHD.

Paradoxical Psoriasis.

Cytokine blocking therapies have revolutionized the management of psoriasis and atopic dermatitis but can lead to the development of paradoxic psoriasis (PP). Patients treated with biologics should be closely monitored for the development of PP and other paradoxical eruptions (including inflammatory joint disease, inflammatory bowel disease, eczematous eruptions, lupus like eruptions, sarcoidal eruptions, and others) and occasionally the development of cutaneous T-cell lymphoma. Further understanding the immunologic mechanism of these processes will ultimately drive our understanding of and ability to predict and manage PPs.

IL17A mRNA Staining Distinguishes Palmoplantar Psoriasis from Hyperkeratotic Palmoplantar Eczema in Diagnostic Skin Biopsies.

Acral dermatoses, including hyperkeratotic palmoplantar eczema (HPE), palmoplantar psoriasis (PP), and mycosis fungoides palmaris et plantaris (MFPP), can be challenging to diagnose clinically and histopathologically. In this setting, cytokine biomarkers may be able to help provide diagnostic clarity. Therefore, we evaluated IL-17A, IFN-γ, and IL-13 expression in PP, HPE, and MFPP and compared their expression profiles with nonacral sites. We used biopsy specimens from the Yale Dermatopathology database, selecting cases of HPE (n = 12), PP (n = 8), MFPP (n = 8), normal acral skin (n = 9), nonacral eczema (n = 10), and nonacral psoriasis (n = 10) with classic clinical and histopathologic features. IL17A mRNA expression by RNA in situ hybridization differentiated PP (median score 63.1 [interquartile range 9.4-104.1]) from HPE (0.8 [0-6.0]; P = 0.003), MFPP (0.6 [0-2.6]; P = 0.003), and normal acral skin (0 [0-0]; P < 0.001). Unexpectedly, both PP and HPE showed co-expression of IFNG and IL13 mRNA. In contrast, nonacral psoriasis and eczema showed divergent patterns of IFNG and IL13 mRNA expression. Taken together, we show that IL17A mRNA expression may be a useful biomarker of PP, and we further show that acral dermatoses exhibit distinct immunology compared to nonacral sites, with implications for clinical management.

Characteristics of Esketamine Prescribers Among Medicare Beneficiaries in the United States, 2019-2020.

This cross-sectional study examines the characteristics and geographic distribution of eskatamine prescribers among Medicare beneficiaries in the US from 2019 to 2020.

Association of sarcoidosis with psoriasis: a cross-sectional study in the All of Us research program.

Psoriasis and sarcoidosis are inflammatory skin and systemic diseases that may share a similar immunopathogenesis involving a Th1 and/or Th17 polarized immune response. Although the coexistence of sarcoidosis and psoriasis in the same individuals has been reported, the potential association between these diseases at a population-level in the United States has not been evaluated. To evaluate this association, we performed a matched cross-sectional study in the All of Us research program database. In the multivariable analysis of 4932 psoriasis cases and 19,728 controls, sarcoidosis was found to be significantly associated with psoriasis (OR 2.37 [95% CI 1.73-3.23], p < 0.001). The relative strength of this association between psoriasis and sarcoidosis may be, in part, explained by overlapping immunopathogenesis and common genetic susceptibility of these diseases. Taken together, these observations underscore the need for screening psoriasis patients for development of new cardiopulmonary symptoms. Further research into the mechanism of this relationship and its implications is warranted.

Autoimmune comorbidities associated with sarcoidosis: a case-control study in the All of Us research program.

Objective: The degree to which sarcoidosis patients are affected by autoimmune diseases is poorly understood. Prior studies of autoimmune co-morbidities in sarcoidosis have focused on populations outside the USA or have been impeded by small sample sizes and limited scope. This case-control study evaluated the association between sarcoidosis and autoimmune diseases in a large, diverse cohort based in the USA. Methods: We used data from the All of Us research programme to conduct a case-control study involving patients ≥18 years old, from 2018 to the present, diagnosed with sarcoidosis. Sarcoidosis cases and age-, sex- and race-matched controls were identified in a 1:4 ratio. Autoimmune co-morbidities were compared between sarcoidosis patients and controls in univariable and multivariable analyses using logistic regression. The degree of association was measured using the odds ratio (OR). Results: A total of 1408 sarcoidosis cases and 5632 controls were included in this study. Seven of 24 examined autoimmune diseases were significantly associated with sarcoidosis in our multivariable analysis (P < 0.05). The composite variable of any autoimmune disease was also significantly associated with sarcoidosis (OR = 2.29, P < 0.001). Conclusion: We demonstrate an association between sarcoidosis and multiple autoimmune diseases in a large and diverse cohort based in the USA. These results underscore the need for careful screening of sarcoidosis patients for concomitant autoimmune disease.

Inhibition of type 1 immunity with tofacitinib is associated with marked improvement in longstanding sarcoidosis.

Sarcoidosis is an idiopathic inflammatory disorder that is commonly treated with glucocorticoids. An imprecise understanding of the immunologic changes underlying sarcoidosis has limited therapeutic progress. Here in this open-label trial (NCT03910543), 10 patients with cutaneous sarcoidosis are treated with tofacitinib, a Janus kinase inhibitor. The primary outcome is the change in the cutaneous sarcoidosis activity and morphology instrument (CSAMI) activity score after 6 months of treatment. Secondary outcomes included change in internal organ involvement, molecular parameters, and safety. All patients experience improvement in their skin with 6 patients showing a complete response. Improvement in internal organ involvement is also observed. CD4+ T cell-derived IFN-γ is identified as a central cytokine mediator of macrophage activation in sarcoidosis. Additional type 1 cytokines produced by distinct cell types, including IL-6, IL-12, IL-15 and GM-CSF, also associate with pathogenesis. Suppression of the activity of these cytokines, especially IFN-γ, correlates with clinical improvement. Our results thus show that tofacitinib treatment is associated with improved sarcoidosis symptoms, and predominantly acts by inhibiting type 1 immunity.

Factors associated with declaration of disability in medical students and junior doctors, and the association of declared disability with academic performance: observational study using data from the UK Medical Education Database, 2002-2018 (UKMED54).

OBJECTIVES: To examine factors associated with declaration of disability by medical students and doctors, and the association of declared disability with academic performance. DESIGN: Observational study using record-linked data collected between 2002 and 2018. SETTING: UK Medical Education Database is a repository of data relating to training of medical students and doctors. Disability and other data are record-linked. PARTICIPANTS: All students starting at a UK medical school between 2002 and 2018 (n=135 930). MAIN OUTCOME MEASURES: Declared disability was categorised by the Higher Education Statistics Authority. Outcomes related to undergraduate academic performance included scores in the educational performance measure (EPM), prescribing safety assessment and situational judgement test. Performance in postgraduate examinations was studied, as well as prior attainment in school examinations and aptitude tests. RESULTS: Specific learning disability (SLD) was the most commonly declared disability (3.5% compared with the next most commonly declared disability at 1.0% of n=129 345 all cases in the study), and during the period covered by the data, SLD declarations increased from 1.4% (n=6440 for students starting in 2002) to 4.6% (n=8625 for students starting in 2018). In a logistic regression, the following factors predicted recording of SLD on entry to medical school ((exp(B)±95% CI), p<0.0001 unless otherwise stated): attendance at a fee-paying school (2.306±0.178), graduate status (1.806±0.205), participation of local areas quintile (1.089±0.030), age (1.034±0.012). First year medical students were less likely to declare SLD if they were from a non-white ethnic background (Asian/Asian British 0.324±0.034, black/black British 0.571±0.102, mixed 0.731±0.108, other ethnic groups 0.566±0.120), female (0.913±0.059; p=0.007) or from a low index of multiple deprivation quintile (0.963±0.029); p=0.017. In univariate analysis with Bonferroni corrections applied for multiple tests, no significant difference was observed in the recording of SLD according to socioeconomic class (χ2=5.637, p=1), whether or not a student's parents had a higher education (χ2=0.140, p=1), or whether or not a student had received a United Kingdom Clinical Aptitude Test (UKCAT) bursary (χ2=7.661, p=0.068). Students who declared SLD at some point in medical school (n=4830) had lower EPM normalised deviate values (-0.390) than those who did not (-0.119) (F=189.872, p<0.001). Those for whom SLD was recorded were as likely to complete the course successfully as those who did not declare disability (93.0% successful completion by those for whom SLD declared from year 1 (n=2480), 92.2% by those for whom SLD declared after year 1 (n=2350), 91.6% by those for whom SD not declared at any point (n=85 180)) (χ2=6.905, p=0.032). Of 3580 first year students who declared SLD, 43.1% had not sat the UKCAT Special Educational Needs aptitude test (which gives extra time for those with special educational needs), while 28% of 2400 registrants for whom SLD was recorded as medical students did not declare it at General Medical Council registration. CONCLUSIONS: Substantial increases in declaration of SLD may reflect changes in the social and legal environment during the period of the study. Those who declare SLD are just as likely to gain a primary medical qualification as those who do not. For some individuals, disability declaration appears to depend on context, based on differences in numbers declaring SLD before, during and after medical school.