Selenium deficiency is associated with polyneuropathy in primary Sjögren's syndrome.

BACKGROUND: Selenium plays an important role in the regulation of the immune system. Selenium deficiency is associated with Hashimoto's thyroiditis, a common comorbidity in primary Sjögren's syndrome (pSS). Therefore we aimed to identify whether or not selenium deficiency is also associated with pSS. METHODS: 107 consecutive female patients with pSS and, as a control, 59 female patients with axial spondyloarthritis were recruited. Later, 11 male pSS patients, 5 of these suffering from polyneuropathy, and 15 male axSpA patients were additionally recruited in order to confirm the results from the female patients. All patients were consulted about their diet and food intolerances and their plasma selenium concentrations were analyzed. Current and previous extraglandular manifestations of pSS were recorded. Patients complaining of misperceptions and tingling paraesthesia underwent measurement of nerve conduction velocity. The proportion of patients and controls with a selenium deficiency was compared using Fisher's exact test. RESULTS: The proportion of female pSS patients with a low selenium concentration <0.63 µmol/L (22.4%) was significantly higher than of the controls (1.7%) (p < 0.001). Within the group of female patients with pSS, selenium deficiency was significantly associated with the presence of polyneuropathy (45.8% with vs 14.5% without polyneuropathy, p = 0.003) and particularly polyneuropathy with motor nerve involvement measured by nerve conduction velocity (41.7% with vs 10.8% without motor neuropathy, p = 0.001). The mean selenium concentrations of the 5 male pSS patients with polyneuropathy were significantly lower compared to the 6 pSS patients without polyneuropathy and to the 15 male axSpA controls. CONCLUSIONS: PSS and in particular its complication polyneuropathy is associated with selenium deficiency. Measurement of the selenium concentration in blood is advisable in patients with pSS and in particular in the subset of patients with polyneuropathy. Substitution of selenium may be a possible therapy of polyneuropathy associated with pSS.

Mortality and guideline-directed medical therapy in real-world heart failure patients with reduced ejection fraction.

OBJECTIVE: To estimate the prevalence of guideline-directed medical therapy (GDMT) in commercially insured US patients with heart failure with reduced ejection fraction (HFrEF) and examine the effect of GDMT on all-cause mortality. GDMT for HFrEF includes pharmacologic therapies such as ß-blockers (BB), angiotensin-converting enzyme inhibitors (ACE-I), angiotensin receptor blockers (ARB), angiotensin receptor-neprilysin (ARNI), mineralocorticoid receptor antagonists (MRA), and sodium-glucose cotransporter inhibitors to reduce morbidity and mortality. METHODS: Patients in the Optum Integrated File from 2007 to 2019Q3, ≥18 years, with history of HFrEF, were identified. Patients prescribed both a BB and either an ACE-I, ARB, or ARNI during 6-month post-diagnosis were assigned to the GDMT cohort. All others were assigned to the not on GDMT cohort. The GDMT cohort was further classified by those patients with a record of prescription fills for both classes of medications concurrently (GDMT concurrent medication fills). Mortality at 2 years was assessed with a Cox regression model accounting for baseline demographics, comorbidities, and diuretic use. RESULTS: This study identified 14 880 HFrEF patients, of which 70% had a record of GDMT, and 57% had a record of concurrent prescriptions. Patients in the not on GDMT cohort had 29% increased risk of mortality versus GDMT (hazard ratio 1.29; 95% CI (1.19-1.40); p < .0001). As a sensitivity analysis, the effect of patients not on GDMT compared to GDMT with concurrent medication fills was more pronounced, with a 37% increased mortality risk. CONCLUSION: In a real-world population of HFrEF patients, inadequate GDMT confers a 29% excess mortality risk over the 2-year follow-up.

Healthcare utilization and guideline-directed medical therapy in heart failure patients with reduced ejection fraction.

Aim: This study examines the effect of guideline-directed medical therapy (GDMT) on healthcare utilization in patients with heart failure with reduced ejection fraction from Optum® Integrated File from 1 January 2007 to 30 June 2020. Materials & methods: Patients with both a beta blocker and either an ACE inhibitor (ACE-I), angiotensin receptor blocker (ARB) or angiotensin receptor neprilysin inhibitor were assigned to the GDMT cohort. All others were not on GDMT. Results: Estimated annual all cause hospitalizations and emergency department visits per 100 patients was 29% (80 vs 62 patients) and 26% higher (54 vs 43 patients; p < 0.0001) and annualized hospital days were longer (1.88 vs 1.64; p = 0.0020) for patients not on GDMT. Conclusion: In a real-world population, heart failure with reduced ejection fraction, patients not optimally managed on GDMT had higher annualized healthcare utilization when compared with patients on GDMT.

Current recommendations for cancer surveillance in Gorlin syndrome: a report from the SIOPE host genome working group (SIOPE HGWG).

Gorlin syndrome (MIM 109,400), a cancer predisposition syndrome related to a constitutional pathogenic variation (PV) of a gene in the Sonic Hedgehog pathway (PTCH1 or SUFU), is associated with a broad spectrum of benign and malignant tumors. Basal cell carcinomas (BCC), odontogenic keratocysts and medulloblastomas are the main tumor types encountered, but meningiomas, ovarian or cardiac fibromas and sarcomas have also been described. The clinical features and tumor risks are different depending on the causative gene. Due to the rarity of this condition, there is little data on phenotype-genotype correlations. This report summarizes genotype-based recommendations for screening patients with PTCH1 and SUFU-related Gorlin syndrome, discussed during a workshop of the Host Genome Working Group of the European branch of the International Society of Pediatric Oncology (SIOPE HGWG) held in January 2020. In order to allow early detection of BCC, dermatologic examination should start at age 10 in PTCH1, and at age 20 in SUFU PV carriers. Odontogenic keratocyst screening, based on odontologic examination, should begin at age 2 with annual orthopantogram beginning around age 8 for PTCH1 PV carriers only. For medulloblastomas, repeated brain MRI from birth to 5 years should be proposed for SUFU PV carriers only. Brain MRI for meningiomas and pelvic ultrasound for ovarian fibromas should be offered to both PTCH1 and SUFU PV carriers. Follow-up of patients treated with radiotherapy should be prolonged and thorough because of the risk of secondary malignancies. Prospective evaluation of evidence of the effectiveness of these surveillance recommendations is required.

Current recommendations for clinical surveillance and genetic testing in rhabdoid tumor predisposition: a report from the SIOPE Host Genome Working Group.

The rhabdoid tumor (RT) predisposition syndromes 1 and 2 (RTPS1 and 2) are rare genetic conditions rendering young children vulnerable to an increased risk of RT, malignant neoplasms affecting the kidney, miscellaneous soft-part tissues, the liver and the central nervous system (Atypical Teratoid Rhabdoid Tumors, ATRT). Both, RTPS1&2 are due to pathogenic variants (PV) in genes encoding constituents of the BAF chromatin remodeling complex, i.e. SMARCB1 (RTPS1) and SMARCA4 (RTPS2). In contrast to other genetic disorders related to PVs in SMARCB1 and SMARCA4 such as Coffin-Siris Syndrome, RTPS1&2 are characterized by a predominance of truncating PVs, terminating transcription thus explaining a specific cancer risk. The penetrance of RTPS1 early in life is high and associated with a poor survival. However, few unaffected carriers may be encountered. Beyond RT, the tumor spectrum may be larger than initially suspected, and cancer surveillance offered to unaffected carriers (siblings or parents) and long-term survivors of RT is still a matter of discussion. RTPS2 exposes female carriers to an ill-defined risk of small cell carcinoma of the ovaries, hypercalcemic type (SCCOHT), which may appear in prepubertal females. RT surveillance protocols for these rare families have not been established. To address unresolved issues in the care of individuals with RTPS and to propose appropriate surveillance guidelines in childhood, the SIOPe Host Genome working group invited pediatric oncologists and geneticists to contribute to an expert meeting. The current manuscript summarizes conclusions of the panel discussion, including consented statements as well as non-evidence-based proposals for validation in the future.

Comparison of Survival in Patients With Clinically Significant Tricuspid Regurgitation With and Without Heart Failure (From the Optum Integrated File).

This study aimed to quantify survival rates for patients with tricuspid regurgitation (TR) using real-world data. Several clinical conditions are associated with TR, including heart failure (HF), other valve disease (OVD), right-sided heart disease (RSHD), and others that impact mortality. Optum data from January 1, 2007, through December 31, 2018 included patients age ≥18 years with TR and 12 months of continuous health plan enrollment before TR. Exclusion criteria were end-stage renal disease or known/primary organ pathology. Cohorts were created hierarchically: (1) TR with HF; (2) TR with OVD (no HF); (3) TR with RSHD only (no OVD or HF); (4) TR only. Survival was estimated using a Cox hazard model with an interaction term for TR severity and adjusted for patient demographics and Elixhauser co-morbidities. A total of 33,686 met study inclusion (1) TR with HF (26.6%); (2) TR with OVD (36.7%); (3) TR with RSHD only (17.1%); (4) TR only (19.6%). TR patients (regardless of severity) with HF, OVD or RSHD had an increased risk of mortality compared with patients with TR alone. TR severity was also significantly associated (hazard ratio = 1.33; p = 0.0002) with an increased risk of all-cause mortality. In conclusion, TR severity is significantly associated with an increased risk of all-cause mortality, independent of associated conditions including HF, OVD, or RSHD. In patients with severe TR, the mortality risk is most pronounced for patients who had RSHD without HF or OVD before their TR diagnosis.

Healthcare utilization in clinically significant tricuspid regurgitation patients with and without heart failure.

Aim: This study evaluated how the presence of right-sided heart disease (RSHD), other valve disease (OVD) and heart failure (HF) impacts healthcare utilization in patients with tricuspid valve disease (tricuspid regurgitation [TR]). Materials & methods: Of the 33,686 patients with TR: 6618 (19.6%) had TR-only; 8952 (26.6%) had TR with HF; 12,367 (36.7%) had TR with OVD but no HF; and 5749 (17.1%) had TR with RSHD only. Results: The presence of RSHD, OVD or HF in patients with TR was independently associated with increased annualized hospitalizations, hospital days and costs relative to patients with TR alone. Conclusion: All three co-morbidities were associated with increased healthcare utilization, with HF showing the greatest impact across all measures.

Pulmonary Hypertension: A Brief Guide for Clinicians.

Pulmonary hypertension (PH) is classified into 5 clinical subgroups: pulmonary arterial hypertension (PAH), PH due to left-sided heart disease, PH due to chronic lung disease, chronic thromboembolic PH (CTEPH), and PH with an unclear and/or multifactorial mechanisms. A range of underlying conditions can lead to these disorders. Overall, PH affects approximately 1% of the global population, and over half of patients with heart failure may be affected. Cardiologists are therefore likely to encounter PH in their practice. Routine tests in patients with symptoms and physical findings suggestive of PH include electrocardiography, chest radiography, and pulmonary function tests. Transthoracic echocardiography is used to estimate the probability of PH. All patients with suspected or confirmed PH, without confirmed left-sided heart or lung diseases, should have a ventilation-perfusion scan to exclude CTEPH. Right-sided heart catheterization is essential for accurate diagnosis and classification. All patients with PAH or CTEPH must be referred to a specialist center. Surgical pulmonary endarterectomy is the treatment of choice for eligible patients with CTEPH. Targeted treatments (phosphodiesterase type 5 inhibitors, soluble guanylate cyclase stimulators, endothelin receptor antagonists, prostacyclin analogues, and prostacyclin receptor agonists) are licensed for patients with PAH. The soluble guanylate cyclase stimulator riociguat is the only licensed targeted therapy for patients with inoperable or persistent/recurrent CTEPH. Management of PH resulting from left-sided heart disease primarily involves treatment of the underlying condition.

Impact of mitral regurgitation on cardiovascular hospitalization and death in newly diagnosed heart failure patients.

AIMS: Heart failure (HF) carries a poor prognosis, and the impact of concomitant mitral regurgitation (MR) is not well understood. This analysis aimed to estimate the incremental effect of MR in patients newly diagnosed with HF. METHODS AND RESULTS: Data from the IBM® MarketScan® Research Databases were analysed. Included patients had at least one inpatient or two outpatient HF claims. A 6 month post-period after HF index was used to capture MR diagnosis and severity. HF patients were separated into three cohorts: without MR (no MR), not clinically significant MR (nsMR), and significant MR (sMR). Time-to-event analyses were modelled to estimate the clinical burden of disease. The primary outcome was a composite endpoint of death or cardiovascular (CV)-related admission. Secondary outcomes were death and CV hospitalization alone. All models controlled for baseline demographics and co-morbidities. Patients with sMR were at significantly higher risk of either death or CV admission compared with patients with no MR [hazard ratio (HR) 1.26; 95% confidence interval (CI) 1.15-1.39]. When evaluating death alone, patients with sMR had significantly higher risk of death (HR 1.24; 95% CI 1.08-1.43) compared with patients with no MR. When evaluating CV admission alone, patients with MR were at higher risk of hospital admission vs. patients with no MR, and the magnitude was dependent upon the MR severity: sMR (HR 1.55; 95% CI 1.38-1.74) and nsMR (HR 1.23; 95% CI 1.08-1.40). CONCLUSIONS: Evidence of MR in retrospective claims significantly increases the clinical burden of incident HF patients. Time to death and CV hospitalizations are increased when MR is clinically significant.

The economic impact of clinically significant tricuspid regurgitation in a large, administrative claims database.

Aim: This study aimed to quantify the healthcare burden of clinically significant tricuspid regurgitation (TR) in patients with and without heart failure (HF).Materials and Methods: Data were from the IBM MarketScan Research Databases from October 2011 to September 2016. Eligible patients met the following inclusion criteria: age ≥18 with a TR diagnosis, 12 months pre (baseline), and 6 months post (landmark) medical enrollment. The landmark period was used to categorize TR severity, defined as a record of pulmonary hypertension with ascites, lower extremity edema or hepatic insufficiency, or tricuspid valve surgery. Cohorts were defined based on TR etiology and severity: (1) no HF and no clinically significant TR; (2) HF with no clinically significant TR; (3) no HF with clinically significant TR; and (4) HF with clinically significant TR. Outcomes of interest were all-cause hospitalizations, hospital days, and expenditures. Multivariable models were fit for each of the annualized outcomes and adjusted for patient demographics, comorbidities, and other concomitant valve diseases.Results: There were 92,994 patients eligible for analysis. Patients with no HF and no clinically significant TR had the annualized healthcare burden of 0.20 all-cause hospitalizations (approximately one inpatient hospitalization every 5 years), 1.07 hospital days, and $17,478 in expenditures. The presence of clinically significant TR, alone or with HF, significantly increased healthcare utilization and expenditures. For patients with no HF with clinically significant TR, the annualized economic burden increased to 0.41 all-cause hospitalizations, 3.13 hospital days, and $29,985 in expenditures. For patients with HF and clinically significant TR, the annualized economic burden was even greater with 0.59 all-cause hospitalizations, 4.31 hospital days, and $42,255 in expenditures.Conclusion: The presence of clinically significant TR is associated with an increase in healthcare utilization and expenditures, irrespective of the presence of HF.

Twelve-month healthcare utilization and expenditures in Medicare fee-for-service patients with clinically significant mitral regurgitation.

Aim: This study sought to quantify the healthcare burden of Medicare patients with clinically significant mitral regurgitation (sMR). Materials & methods: Proxy definitions were used for sMR, including MR surgery, atrial fibrillation, pulmonary hypertension or >2 echocardiograms. Results: In this study, 11,173 patients had significant degenerative MR (sDMR); 25,402 had significant functional MR (sFMR); and 12,232 had significant uncharacterized MR (sUMR). Patients with sFMR (18,880) were more likely to be hospitalized and present to the emergency department compared with patients with sDMR (9,795) or sUMR (10,587). Annual healthcare expenditures for sMR patients were: US$29,328 for sFMR; US$17,112 for sUMR; and US$12,870 for sDMR. Conclusion: Novel therapeutic interventions merit further evaluation to reduce the substantial healthcare burden of sMR in the Medicare population.

The Economic Impact of Mitral Regurgitation on Patients With Medically Managed Heart Failure.

The objective of this study was to quantify the financial healthcare burden of mitral regurgitation (MR) on medically managed heart failure (HF) patients. Data from the Truven Health MarketScan Commercial Claims and Medicare Supplemental Databases were analyzed. Included patients had a minimum of 1 inpatient or 2 outpatient claims for HF with a 6-month preperiod (baseline). A 6-month postperiod (landmark) after HF index was used to capture MR diagnosis and severity. Following the landmark period, patients had to have 12 months of continuous medical and prescription drug plan enrollment with at least 2 records of HF medication refills. A therapeutic intensity score was calculated based on HF medication usage. Medically managed HF patients were separated into 3 cohorts: without MR (no MR), insignificant MR (iMR), and significant MR (sMR). Healthcare utilization and all-cause expenditures were modeled to quantify the burden of MR. All models controlled for baseline demographics, co-morbid conditions, and HF therapeutic intensity. Medically managed incident HF patients with sMR had significantly more hospital days (1.91 vs 1.72 days; p = 0.0096) and annual expenditures ($23,988 vs $21,530; p < 0.0001) compared with no MR patients. No differences were identified when comparing iMR and no MR. When evaluating HF admissions, sMR patients had an estimated 50% greater HF admissions rate (0.036 vs 0.024; p < 0.0001) compared with no MR patients. Additionally, HF admits for iMR were 23% more than those with no MR (0.029 vs 0.024; p = 0.0064). In conclusion, evidence of MR in retrospective claims significantly increases the healthcare impact of medically managed HF patients. Both utilization and financial burden is more pronounced when MR is clinically significant.

The healthcare burden of disease progression in medicare patients with functional mitral regurgitation.

Objective: This retrospective database analysis estimated the incremental effect that disease progression from non-clinically significant functional mitral regurgitation (nsFMR) to clinically significant FMR (sFMR) has on clinical outcomes and costs. Methods: Medicare Fee for Service beneficiaries with nsFMR were examined, defined as those with a heart failure diagnosis prior to MR. Patients were classified as ischemic if there was a history of: CAD, AMI, PCI, or CABG. The primary outcome was time to sFMR, defined as pulmonary hypertension, atrial fibrillation, mitral valve surgery, serial echocardiography, or death, using a Cox hazard regression model. Annualized hospitalizations, inpatient hospital days, and healthcare expenditures were also modeled. Results: Patients with IHD had higher risk (Hazard Ratio = 1.22 [1.14-1.30]) for disease progression compared to patients without. The progression cohort had significantly more annual inpatient hospitalizations (non-IHD = 1.32; IHD = 1.40) than the non-progression cohort (non-IHD = 0.36; IHD = 0.34), and significantly more annual inpatient hospital days (non-IHD = 13.07; IHD = 13.52) than the non-progression cohort (non-IHD = 2.29; with IHD = 2.08). The progression cohort had over 3.5-times higher costs vs the non-progression cohort, independent of IHD (non-IHD = $12,798 vs $46,784; IHD = $12,582 vs $49,348). Conclusion: Treating FMR patients earlier in their clinical trajectory may prevent disease progression and reduce high rates of healthcare utilization and expenditures.

Axonal myelin decrease in the splenium in major depressive disorder.

The corpus callosum has become a key area of interest for researchers in severe mental illness. Disruptions in fractional anisotropy in the callosum have been reported in schizophrenia and major depressive disorder. No change has been reported in oligodendrocyte density and overall size of the callosum in either illness, suggesting that gross morphology is unchanged, but subtler organisational disruption may exist within this structure. Using high-resolution oil immersion microscopy, we examined the cross-sectional area of the nerve fibre and the axonal myelin sheath; and using standard high-resolution light microscopy, we measured the density of myelinated axons. These measurements were made in the splenium of the corpus callosum. Measures were taken in the sagittal plane in the callosal splenium to contrast with the previous similar examination of the callosal genu. Cases of major depressive disorder had significantly decreased mean myelin cross-sectional area (p = 0.014) per axon in the splenium than in controls or schizophrenia groups. There was no significant change in the density of myelinated axons. The results suggest a clear decrease of myelin in the axons of the callosal splenium in MDD, although this type of neuropathological study is unable to clarify whether this is caused by changes during life or has a developmental origin. In contrast with increased myelin in the callosal genu, this result suggests a longitudinal change in callosal myelination in major depressive disorder not present in normal or schizophrenic brains.

Caso de desafío diagnóstico: fístula dural / Diagnostic challenge case: dural fistula

Se presenta el caso de una paciente de sexo femenino, de 69 años, que refiere tinnitus pulsátil de dos meses de evolución percibido en la región retroauricular derecha. Se presentan los hallazgos en estudios de imágenes, diagnóstico y se presenta una corta revisión del tema.

We present the case of a female patient, 69 years old, who reported pulsatile tinnitus since two months ago perceived in the right retroauricular region. We present the findings in image studies, diagnosis and a short review about the topic.

Mathematical modeling of Myosin induced bistability of Lamellipodial fragments.

For various cell types and for lamellipodial fragments on flat surfaces, externally induced and spontaneous transitions between symmetric nonmoving states and polarized migration have been observed. This behavior is indicative of bistability of the cytoskeleton dynamics. In this work, the Filament Based Lamellipodium Model (FBLM), a two-dimensional, anisotropic, two-phase continuum model for the dynamics of the actin filament network in lamellipodia, is extended by a new description of actin-myosin interaction. For appropriately chosen parameter values, the resulting model has bistable dynamics with stable states showing the qualitative features observed in experiments. This is demonstrated by numerical simulations and by an analysis of a strongly simplified version of the FBLM with rigid filaments and planar lamellipodia at the cell front and rear.

Comprendiendo las fracturas triplanares de la tibia distal / Understanding triplane distal tibia fractures

Abstract. Triplane fractures (TF) are a special type of fracture that typically occur in the distal tibia, in a specific age group, and require specific treatment. It should be diagnosed early to avoid complications and irreparable consequences. Imaging techniques play a fundamental role. A review of TF is performed, and cases are presented in order to understand how they occur, and thus diagnose them properly.

Resumen. Las fracturas triplanares (FT) son un tipo especial de fracturas que se producen clásicamente en la tibia distal, en un grupo etario acotado y que requieren un tratamiento específico. Su diagnóstico debe ser oportuno para evitar complicaciones y secuelas irreparables, por lo que las imágenes cumplen un rol fundamental. Se realiza una revisión sobre las FT y una muestra de casos para comprender cómo se generan y así realizar un adecuado diagnóstico de ellas.

Premature loss of muscle mass and function in type 2 diabetes.

INTRODUCTION: Muscle mass and function are among the most relevant factors that contribute to an optimal quality of life, and are strong predictors of mortality in the elderly. Loss of lean tissues and deterioration of muscle function have been described as one of the many complications of type 2 diabetes mellitus (DM2), but most studies do not isolate age as an intervening factor. AIM: To study whether adult DM2 patients up to 60years of age have decreased muscle mass and function compared with healthy non-diabetic (ND) subjects of similar age. METHODOLOGY: Appendicular fat-free mass (ApFFM) by dual X-ray absorptiometry (DEXA), handgrip strength (HS), quadriceps strength (QS), 12 min walking capacity (12MW) and the Timed Up and Go test (TUG) were measured in 100 DM2 patients and 39 ND controls. Muscle quality, or the ratio between lean mass and muscle strength of upper and lower limbs, and the functional limitations associated with pain and stiffness assessed according to the Western Ontario and McMaster Universities Arthrosis Index (WOMAC) were also recorded. Specific tests were performed to rule out microvascular diabetic complications (retinal and peripheral nerves), metabolic control, kidney function and vitamin D status and examine their association with ApFFM and function. RESULTS: ApFFM was significantly higher among DM2 female patients and lower among diabetic men. However opposite results were obtained when individual values were corrected for body mass index (BMI), specifically among women, who were more likely to be obese. As for muscle strength and global functionality tests, significantly better performances in TUG, 12MW, QS and HS were observed among ND subjects of both sexes. These differences prevailed even after excluding diabetic patients with microvascular complications as well as those with more than 10years of diabetes. Muscle quality was also significantly better among ND women. Higher scores of pain and stiffness in the WOMAC scale correlated with 12MW and TUG in both groups but did not correlate with ApFFM. CONCLUSIONS: We found a clear deterioration of lean mass and muscle functions among adult DM2 patients of up to 60years old, independent of length of disease, metabolic control, vitamin D status and presence of microvascular complications and pain.