Characterization of the thymus in Lrp4 myasthenia gravis: Four cases

Myasthenia gravis (MG) is an autoimmune disease of the neuromuscular junction. Most patients have pathogenic autoantibodies against the acetylcholine receptor (AChR). In the last years a novel subpopulation of MG patients has been described that harbors antibodies against low-density lipoprotein receptor-related protein 4 (Lrp4), another postsynaptic neuromuscular antigen. In early-onset AChR MG (EOMG), the thymus plays an important role in immunopathogenesis, and early thymectomy is beneficial. It is still unknown if the thymus plays any role in Lrp4-MG. In this pilot study, we compared thymus samples from four patients with Lrp4-MG (one pre-treated with immunosuppressive drugs), four non-MG controls and five EOMG patients (not pretreated with immunosuppressive drugs). Immunohistochemistry of the Lrp4-MG thymi revealed normal architecture, with normal numbers and distribution of B-cells, lymphoid follicles and Hassall's corpuscles. Primary CD23⁺ lymphoid follicles were similarly infrequent in Lrp4-MG and control thymic sections. In none of the control or Lrp4-MG thymi did we find secondary follicles with CD10⁺ germinal centers. These were evident in 2 of the 5 EOMG thymi, where primary lymphoid follicles were also more frequent on average, thus showing considerable heterogeneity between patients. Even if characteristic pathological thymic changes were not observed in the Lrp4 subgroup, we cannot exclude a role for the thymus in Lrp4-MG pathogenesis, since one Lrp4-MG patient went into clinical remission after thymectomy alone (at one year follow-up) and one more improved after thymectomy in combination with immunosuppressive therapy.     

Renal Mechanisms of Association between Fibroblast Growth Factor 1 and Blood Pressure

The fibroblast growth factor 1 (FGF1) gene is expressed primarily in the kidney and may contribute to hypertension. However, the biologic mechanisms underlying the association between FGF1 and BP regulation remain unknown. We report that the major allele of FGF1 single nucleotide polymorphism rs152524 was associated in a dose-dependent manner with systolic BP (P=9.65×10⁻⁵) and diastolic BP (P=7.61×10⁻³) in a meta-analysis of 14,364 individuals and with renal expression of FGF1 mRNA in 126 human kidneys (P=9.0×10⁻³). Next-generation RNA sequencing revealed that upregulated renal expression of FGF1 or of each of the three FGF1 mRNA isoforms individually was associated with higher BP. FGF1-stratified coexpression analysis in two separate collections of human kidneys identified 126 FGF1 partner mRNAs, of which 71 and 63 showed at least nominal association with systolic and diastolic BP, respectively. Of those mRNAs, seven mRNAs in five genes (MME, PTPRO, REN, SLC12A3, and WNK1) had strong prior annotation to BP or hypertension. MME, which encodes an enzyme that degrades circulating natriuretic peptides, showed the strongest differential coexpression with FGF1 between hypertensive and normotensive kidneys. Furthermore, higher level of renal FGF1 expression was associated with lower circulating levels of atrial and brain natriuretic peptides. These findings indicate that FGF1 expression in the kidney is at least under partial genetic control and that renal expression of several FGF1 partner genes involved in the natriuretic peptide catabolism pathway, renin-angiotensin cascade, and sodium handling network may explain the association between FGF1 and BP.     

Transient Effects of Anesthesia on Leukocyte Apoptosis and Monocyte Cytokine Stimulation: A Clinical Study

The effects of anesthetics on immune cell apoptosis and cytokine stimulation were studied in a prospective study. American Society of Anesthesiologists I/II patients underwent elective inguinal hernia repair or varicose veins stripping surgery and were randomized to either epidural anesthesia (n = 14) or general anesthesia with sevoflurane (n = 19) or propofol (n = 15). Blood was sampled before anesthesia induction (T0), at the end of surgery (T1), and 6 h later (T2). Apoptosis was determined by ANNEXIN-V staining of white blood cells; monocytes were isolated and stimulated for cytokine production. Results were compared with 10 healthy volunteers well-matched for age and gender. Apoptosis of lymphocytes and monocytes was increased in the epidural and sevoflurane groups at T2. Propofol group had increased production of interleukin-6 at T1 and sevoflurane and epidural groups had decreased production of tumor necrosis factor-alpha at T2. Results emphasize the modulation of immune function by epidural and sevoflurane but not propofol anesthesia in a clinical setting.     

Contribution of computed tomography guided percutaneous drainage of tuberculous cold abscesses adjunctive to pharmaceutical anti-tubercular treatment

Purpose

To determine the efficiency and safety of the percutaneous aspiration and drainage of rare touberculous cold abscesses under CT guidance.

Materials and methods

We retrospectively studied 63 cases of 44 patients, treated in our hospital during the last two years. They suffered from tuberculous infection complicated with tuberculous cold abscesses variously located. All these patients underwent percutaneous aspiration and drainage under CT imaging, following the trocar puncture technique. The catheter remained in place for about a week. A follow up CT scan was performed in all cases before the catheter removal. Some of the patients were under anti tuberculosis medication.

Results

All the patients had a successful recovery from the abscesses. There were no major or minor complications observed. No recurrence occurred until today.

Conclusion

CT guided percutaneous aspiration and drainage of tuberculous cold abscesses is a safe, minimal invasive and effective method of treatment. Drainage and specific antituberculosis therapy leads to a satisfactory conclusion.     

Basal ganglia hyperintensity on T1-weighted MRI in Rendu-Osler-Weber disease

The purpose of this study was to evaluate possible central nervous system (CNS) involvement in Rendu-Osler-Weber (ROW) disease in magnetic resonance imaging (MRI). Three patients with symptomatic ROW disease underwent brain MRI. Brain MRI depicted in all three of them increased signal intensity on T1-weighted images involving the globus pallidus and cerebral crura bilaterally. Laboratory studies of the two men showed iron deficiency anemia, while all three of them had normal liver function tests and increased manganese blood concentration. Gastroscopy and colonoscopy revealed a gastric and a cecal arteriovenous malformation (AVM) in the first one, while pulmonary and hepatic computed tomography (CT) angiography did not detect any intrahepatic shunts. Liver ultrasound in the second one revealed dilatation of intrahepatic artery branches consistent with intrahepatic shunts, while it was normal in the third patient. Chest radiographs were normal in all three patients. Pallidal T1 hyperintensity on T1-weighted imaging may be a biomarker of manganese overload in ROW disease.     

Infection complications after transrectal ultrasound-guided prostate biopsy: A radiology department’s experience and strategy for improvement

IntroductionTransrectal ultrasound (TRUS)-guided prostate biopsy is a common procedure performed to diagnose prostate cancer. The risk of infection complications is well-described in the literature, and strategies to avoid such complications continue to evolve over time. We performed a retrospective review of our infection complications and propose a strategy for improvement.MethodsWe reviewed clinical outcomes from patients undergoing TRUS-guided prostate biopsy at our institution from November 2018 to November 2020. We reported the antimicrobial prophylaxis received, whether the biopsy was systematic or targeted, and we examined the rate of clinically significant infection complications and hospitalization.ResultsAmong 312 men who underwent TRUS-guided prostate biopsy during the study period, seven (2.2%) had an infection. Four patient groups with distinct antimicrobial regimen were identified; the largest of these patient groups received a three-day course of cefixime and a single dose of fosfomycin (59%). The proportion of patients with infection complications across these groups did not demonstrate a statistically significant difference (p=0.803). There was no significant difference in proportion of infection between systematic and targeted biopsy groups (3.0% vs. 0%, p=0.204). The proportion of patients hospitalized was 1.3%, with a mean length of stay of four days.ConclusionsWe report a rate of clinically significant infection following TRUS-guided prostate biopsy of 2.2%. Due to our referral pathway, we have an inconsistent approach to antimicrobial prophylaxis, although there was no statistically significant difference in infection rate between the groups. We propose a standardized approach that may lead to improved patient outcomes.     

Time experience in patients with schizophrenia and affective disorders

BackgroundThe experience of time, or the temporal order of external and internal events, is essential for humans. In psychiatric disorders such as depression and schizophrenia, impairment of time processing has been discussed for a long time.AimsIn this explorative pilot study, therefore, the subjective time feeling as well as objective time perception were determined in patients with depression and schizophrenia, along with possible neurobiological correlates.MethodsDepressed (n = 34; 32.4 ± 9.8 years; 21 men) and schizophrenic patients (n = 31; 35.1 ± 10.7 years; 22 men) and healthy subjects (n = 33; 32.8 ± 14.3 years; 16 men) were tested using time feeling questionnaires, time perception tasks and critical flicker-fusion frequency (CFF) and loudness dependence of auditory evoked potentials (LDAEP) to determine serotonergic neurotransmission.ResultsThere were significant differences between the three groups regarding time feeling and also in time perception tasks (estimation of given time duration) and CFF (the “DOWN” condition). Regarding the LDAEP, patients with schizophrenia showed a significant negative correlation to time experience in terms of a pathologically increased serotonergic neurotransmission with disturbed time feeling.ConclusionsImpairment of time experience seems to play an important role in depression and schizophrenia, both subjectively and objectively, and novel neurobiological correlates have been uncovered. It is suggested, therefore, that alteration of experience of time should be increasingly included in the current psychopathological findings.     

The Longitudinal Association of Lifestyle with Cognitive Health and Dementia Risk: Findings from the HELIAD Study

The aim of the current study was to investigate whether a Total Lifestyle Index (TLI), including adherence to the Mediterranean diet, sleep duration, physical activity and engagement in activities of daily living, is associated with cognitive health over time and dementia risk, in a representative cohort of older people. A total of 1018 non-demented community-dwelling older adults ≥65 years old (60% women) from the HELIAD study were included. A comprehensive neurological and neuropsychological assessment was conducted at baseline and at the 3-year follow-up evaluating cognitive functioning, and a dementia diagnosis was set. Diet, physical activity, sleep duration and engagement in activities of daily living were assessed using standard, validated questionnaires at baseline. Sixty-one participants developed dementia at follow-up; participants who developed dementia were older and had fewer years of education compared with participants with normal cognition. With the exception of sleep duration, participants with normal cognition at follow-up scored higher in the individual lifestyle factors compared to those who developed dementia. Regarding TLI, values were lower for participants with dementia compared with those with normal cognition. Each additional unit of the TLI was associated with 0.5% of a standard deviation less decline per year of the Global Cognition score, whereas for each additional unit of the TLI, the risk for dementia was reduced by 0.2% per year (p < 0.05). Our results suggest that greater adherence to a healthy lifestyle pattern is associated with a slower decline of cognitive function and reduced dementia risk.