Selection of disease modifying therapies in multiple sclerosis based on patient's age and disease activity: Data from a nationwide registry.

BACKGROUND: Knowledge of the safety and efficacy of disease-modifying therapies (DMTs) in older patients with Multiple Sclerosis (pwMS) is limited due to their exclusion from clinical trials. Our purpose is to evaluate the choice of DMTs in pwMS older than 50 years old in a real-world setting. METHODS: Cross-sectional study of pwMS from the Argentine MS and NMOSD Registry. We included patients under 35 and above 50 years old prescribed DMTs. Disease activity was categorized as highly active (HA) or not highly active (NHA), and DMTs were classified as low efficacy therapies (LET) or high efficacy therapies (HET). RESULTS: 1460 patients (65% females) were enrolled. The HA group comprised 241 patients, 198 young (82.2%) and 43 older (17.8%). The NHA group included 1219 patients, 893 young (73%) and 326 older (27%). In the NHA group, older patients received LET more frequently than younger patients (66% versus 44%; p < 0.01). In the HA group, older patients received LET in 61% of cases, whereas younger patients received HET in 71% (p = 0.01). CONCLUSION: The study shows the preference of LET in older patients regardless of disease activity. However it does not demonstrate a difference in disability in older patients based on low vs high efficacy DMTs used, probably due to the design of the study. Further longitudinal studies are warranted to address this issue.

Cystic phenotype and chronic kidney disease in autosomal dominant Alport syndrome.

BACKGROUND AND HYPOTHESIS: Autosomal Dominant Alport Syndrome (ADAS), also known as Thin Basement Membrane Disease (TBMD), is caused by pathogenic variants in COL4A3 and COL4A4 genes. A cystic phenotype has been described in some patients with TBMD, but no genetic studies were performed. We conducted a genetic and radiologic investigation in a cohort of ADAS patients to analyze the prevalence of multicystic kidney disease (MKD) and its association with Chronic Kidney Disease (CKD). METHODS: Retrospective single-center cohort study. Thirty-one patients showing pathogenic or likely pathogenic variants in COL4A3 or COL4A4 from a cohort of 79 patients with persistent microscopic hematuria were included. Mean follow-up was 9.4±9.6 years. The primary objective of the study was to determine the prevalence of MKD in the cohort of ADAS patients. Secondary objectives were to determine risk factors associated with an eGFR<45 ml/min/1.73m2 at the time of genetic and radiologic evaluation and to investigate the coexistence of other genetic abnormalities associated with familial hematuria and cystic kidney disease. RESULTS: MKD was found in 16 patients (52%). Mean number of cysts per kidney was 12.7±5.5. No genetic abnormalities were found in a panel of 101 other genes related to familial hematuria, focal segmental glomerulosclerosis and cystic kidney disease. A greater number of patients with MKD had an eGFR<45 ml/min/1.73m2 (63% vs 7%, p=0.006) and more advanced CKD than patients without MKD. The annual rate of eGFR decline was greater in patients with MKD: -1.8 vs 0.06 ml/min/1.73m2/year (p=0.009). By multivariable linear regression analysis, the main determinants of eGFR change per year were time-averaged proteinuria (p=0.002) and MKD (p=0.02). CONCLUSION: MKD is commonly found in ADAS and is associated with a worse kidney outcome. No pathogenic variants were found in genes other than COL4A3/COL4A4.

Achieving no evidence of disease activity-3 in highly active multiple sclerosis patients treated with cladribine and monoclonal antibodies.

Background: We aimed to determine the proportion of highly active multiple sclerosis patients under high-efficacy therapies (HETs) achieve no evidence of disease activity-3 (NEDA-3) at 1 and 2 years, and to identify factors associated with failing to meet no evidence of disease activity 3 at 2 years. Methods: This retrospective cohort study based on Argentina Multiple Sclerosis patient registry (RelevarEM), includes highly active multiple sclerosis patients who received HETs. Results: In total, 254 (78.51%) achieved NEDA-3 at year 1 and 220 (68.12%) achieved NEDA-3 at year 2. Patients who achieved NEDA-3 at 2 years had a shorter duration of multiple sclerosis (p < 0.01) and a shorter time between first treatment and current treatment (p = 0.01). Early high-efficacy strategy patients reached NEDA-3 more frequently (p < 0.01). Being a naïve patient (odds ratio: 3.78, 95% confidence interval 1.50-9.86, p < 0.01) was an independent predictor to reach NEDA-3 at 2 years. No association was found between type of HETs and NEDA-3 at 2 years when adjusted for potential confounders (odds ratio: 1.73; 95% confidence interval 0.51-6.06, p 0.57). Conclusion: We found a high proportion of patients who achieved NEDA-3 at 1 and 2 years. Early high-efficacy strategy patients had a higher probability of achieving NEDA-3 at 2 years.

Siltuximab Monotherapy in Tafro Syndrome: A Case Report and Review of the Literature.

TAFRO syndrome is characterized by the presence of thrombocytopenia, anasarca, fever, reticular myelofibrosis, organomegaly, and is frequently associated with kidney damage in the form of membranoproliferative glomerulonephritis (MPGN) or thrombotic microangiopathy (TMA). Treatment is based on corticosteroids. A 59-year-old man who suffered from heart disease, pancytopenia and hepatosplenomegaly of unknown etiology developed nephrotic syndrome and progressive renal insufficiency, with a kidney biopsy suggestive of MPGN with a "full-house" immunofluorescence pattern. Positron emission tomography (PET) revealed multiple lymphadenopathies which histologically were compatible with multicentric Castleman's disease. The patient was diagnosed with TAFRO syndrome and treatment with siltuximab was started, with evident improvement at 3 months. TAFRO syndrome is a rare entity which may present with severe kidney involvement and histological findings of MPGN or TMA, with or without immune complex deposits. Our case suggests that a corticosteroid-free regimen with siltuximab could be an attractive therapeutic option.

Upper gastrointestinal bleeding secondary to late gastric metastasis of renal cell carcinoma.

Clear cell renal cell carcinoma is the most common renal neoplasm in adults. It has a relatively slow growth pattern that delays diagnosis until the onset of local, paraneoplastic or metastasis-related manifestations, and an unpredictable behavior ranging from aggressive tumors with poor short-term prognosis to late recurrence cases where metastases are identified years after nephrectomy, the latter scenario being the subject of the case we herein report.

PTSD symptomatology is selectively associated with impaired sustained attention ability and dorsal attention network synchronization.

Posttraumatic Stress Disorder (PTSD) symptomatology is associated with dysregulated sustained attention, which produces functional impairments. Performance on sustained attention paradigms such as continuous performance tasks are influenced by both the ability to sustain attention and response strategy. However, previous studies have not dissociated PTSD-related associations with sustained attention ability and strategy, which limits characterization of neural circuitry underlying PTSD-related attentional impairments. Therefore, we characterized and replicated PTSD-related associations with sustained attention ability and response strategy in trauma-exposed Veterans, which guided characterization of PTSD-related differences in neural circuit function. In Study 1, PTSD symptoms were selectively associated with reduced sustained attention ability, but not more impulsive response strategies. In Study 2, we utilized task and resting-state fMRI to characterize neural circuitry underlying PTSD-related differences in sustained attention ability. Both PTSD symptomatology and sustained attention ability exhibited converging associations with reduced dorsal attention network (DAN) synchronization to endogeneous attentional fluctuations. Post-hoc time course analyses demonstrated that PTSD symptoms were most accurately characterized by delayed, rather than globally reduced, DAN synchronization to endogenous attentional fluctuations. Together, these findings suggest that PTSD symptomatology may selectively impair sustained attention ability by disrupting proactive engagement of attentional control circuitry.

Diagnosis of biliary papillomatosis with a Spyglass® cholangioscope.

We report the case of a 78-year-old woman with dyspepsia for several years and a history of cholecystectomy, informed by pathology as calculous cholecystopathy, where CT revealed a left-sided intrahepatic bile duct dilation. Cholangio-MRI confirmed a size increase in the distal intrahepatic bile duct on the left side, with T2-hyperintense contents with scarce contrast enhancement, which resulted in the observed dilation. . A Spybite® forceps was used to obtain a biopsy sample, which showed a benign papillary growth compatible with biliary papillomatosis. Biliary papillomatosis or intraductal papillary neoplasm of the biliary tract is a rare, uncommon condition characterized by intraductal papillary growth of the biliary epithelium. It has a tendency towards malignization, hence must be considered a premalignant condition . Major symptoms include jaundice, abdominal pain, and repeat cholangitis, with imaging studies being key for diagnostic suspicion . The development of cholangioscopy with biopsies allows an early diagnosis of malignant precursor lesions of the bile duct, thus allowing early treatment.

Ethmoidal metastasis as an uncommon presentation and diagnostic form of hepatocellular carcinoma.

Nasopharynx metastases are an extremely rare cause of hepatocarcinoma debut. We report the case of a 71 year old man who presented symptoms of nosebleed and diplopia event, diagnosed by imaging and biopsy of ethmoidal metastasis of hepatocarcinoma.

Endoscopic submucosal dissection of gastric plexiform fibromyxoma, an alternative to the traditional approach.

We report the case of a 62-year-old woman with no history of interest who presented with dyspepsia of 2 years' standing. Gastroscopy revealed a subepithelial lesion at the greater antral curvature with irregular surface and preserved mucosal and vascular pattern, 15 mm in diameter. Because of clinical persistence a radial endoscopic ultrasonogram (EUS) was performed, which showed a well-delimited hypoechoic lesion with heterogeneous areas that was dependent on the muscularis mucosae layer. A biopsy was obtained using the "bite-on-bite" technique, which provided no pathological findings. With these findings an endoscopic submucosal dissection (ESD) procedure was performed with wide margins and no complications. Pathology found low-grade mesenchymal fusicellular proliferation dependent on the muscularis mucosae with immunohistochemistry positive for smooth-muscle vimentin and actin, consistent with plexiform fibromyxoma.

Evaluation of the times of disability progression and related factors in patients with primary progressive multiple sclerosis from Argentina.

Background PPMS (primary progressive multiple sclerosis) patients represent less than 10% of MS patients in Argentina, men and women were similarly affected and most of them had a severe functional impairment. More rapid progression has been reported in males, but this is not the case in all datasets. The main objective of our study was to determine the time to EDSS (Expanded disability Status Scale) 4, 6 and 7 in PPMS patients. We also compared the times to reach these EDSS in men and women and aimed to identify factors associated with the disability progression. Method This cohort of patients with diagnosis of PPMS (n = 253) was selected from follow-up recorded in the RelevarEM registry database. Result The median times to EDSS 4, 6 and 7 were 24 (IQR 12-48), 72 (IQR 36-96) and 96 (IQR 60-120) months, respectively. Comparison of the survival curves to EDSS 4, 6 and 7 according to gender did not show significant differences (p = 0.33, p = 0.55 and p = 0.59). There is no evidence of an association between the clinical adjustment variables (sex, age >40 years at diagnosis, EDSS > 3 at onset and multifocal MS symptoms at disease onset) and the time of arrival at the EDSS 4, 6 and 7. Conclusion Severe disability was observed six years after the onset of symptoms. No association was found between the studied factors and the time to arrival to severe disability.

Capecitabine-induced hyperammonemic encephalopathy.

We report the case of a 79-year-old male who had undergone surgery for a mucus-secreting, stage-III pancreatic adenocarcinoma 2 years previously, who was recently started on capecitabine monotherapy for radiographic local progression. He developed disorientation, asterixis, nausea and elevated serum ammonia (221 µmol/L) 48-72 hours after treatment onset with preserved liver function. After ruling out potential causes of encephalopathy and tumor progression by abdominal and brain CT scans, his symptoms were related by exclusion to the recently initiated treatment with capecitabine. Capecitabine discontinuation, onset of standard anti-encephalopathy measures, and intravenous hydration led to a rapid, complete resolution of symptoms with serum ammonia normalization.