Idiopathic hypertrophic pachymeningitis presenting with occipital neuralgia

BackgroundAlthough occipital neuralgia is usually caused by degenerative arthropathy, nearly 20 other aetiologies may lead to this condition.MethodsWe present the first case report of hypertrophic pachymeningitis revealed by isolated occipital neuralgia.

Results and conclusions

Idiopathic hypertrophic pachymeningitis is a plausible cause of occipital neuralgia and may present without cranial-nerve palsy. There is no consensus on the treatment for idiopathic hypertrophic pachymeningitis, but the usual approach is to start corticotherapy and then to add immunosuppressants. When occipital neuralgia is not clinically isolated or when a first-line treatment fails, another disease diagnosis should be considered. However, the cost effectiveness of extended investigations needs to be considered.     

The acoustic cough monitoring and manometric profile of cough and throat clearing

Cough and throat clearing might be difficult to differentiate when trying to detect them acoustically or manometrically. The aim of this study was to assess the accuracy of acoustic monitoring for detecting cough and throat clearing, and to also determine whether these two symptoms present with different manometric profiles on esophageal pressure topography. Ten asymptomatic volunteers (seven females, mean age 31.1) were trained to simulate cough and throat clearing in a randomized order every 6 minutes during simultaneous acoustic monitoring and high‐resolution manometry. The accuracy of automated acoustic analysis and two blinded reviewers were compared. The pattern of the events and the duration of the pressure changes were assessed using the 30 mmHg isobaric contour. There were 50 cough and 50 throat‐clearing events according to the protocol. The sensitivity and specificity of automated acoustic analysis was 84% and 50% for cough, while the blinded analysis using sound revealed a sensitivity and specificity of 94% and 92%. The manometric profile of both cough and throat clearing was similar in terms of qualitative findings; however, cough was associated with a greater number of repetitive pressurizations and a more vigorous upper esophageal sphincter contraction compared with throat clearing. The acoustic analysis software has a moderate sensitivity and poor specificity to detect cough. The profile of cough and throat clearing in pressure topography revealed a similar qualitative pattern of pressurization with more vigorous pressure changes and a greater rate of repetitive pressurizations in cough.     

Surgical therapy of ground-glass opacities

Ground glass opacities, also known as GGOs, are detected on computed tomography (CT) scans as hazy areas if increased attenuation in the lung, and my represent a variety of pulmonary processes. Natural history of GGOs and their clinical implications are not yet fully understood. Controversies associated with the management of GGOs surround their histological classification, malignant potential, indications, timing, and type of intervention. Herein we discuss the principles and role of surgical therapy for ground glass opacities.     

Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination

Females have generally more robust immune responses than males for reasons that are not well-understood. Here we used a systems analysis to investigate these differences by analyzing the neutralizing antibody response to a trivalent inactivated seasonal influenza vaccine (TIV) and a large number of immune system components, including serum cytokines and chemokines, blood cell subset frequencies, genome-wide gene expression, and cellular responses to diverse in vitro stimuli, in 53 females and 34 males of different ages. We found elevated antibody responses to TIV and expression of inflammatory cytokines in the serum of females compared with males regardless of age. This inflammatory profile correlated with the levels of phosphorylated STAT3 proteins in monocytes but not with the serological response to the vaccine. In contrast, using a machine learning approach, we identified a cluster of genes involved in lipid biosynthesis and previously shown to be up-regulated by testosterone that correlated with poor virus-neutralizing activity in men. Moreover, men with elevated serum testosterone levels and associated gene signatures exhibited the lowest antibody responses to TIV. These results demonstrate a strong association between androgens and genes involved in lipid metabolism, suggesting that these could be important drivers of the differences in immune responses between males and females.The variability in the biology of human populations poses significant challenges in understanding different disease outcomes and developing successful therapeutics. The sources of this variation are likely the consequence of genetics, epigenetics, and the history of antigenic exposure (1, 2). As therapies targeting immune function are developed to improve clinical outcomes in cancer, viral and bacterial infections, autoimmune diseases, and transplantation, identifying the sources of immunological variation and finding biomarkers for immune health and dysfunction are crucial for their success (3).An important source of immunological variation is known to be the sex of the individual. Males experience a greater severity and prevalence of bacterial, viral, fungal, and parasitic infections than females, who also exhibit a more robust response to antigenic challenges such as infection and vaccination (4, 5). This stronger immune response in females could also explain why they more frequently develop immune-mediated pathologies during influenza infection, such as an overproduction of cytokines (cytokine storm) that contribute to an increase in capillary permeability and lung failure (6). Furthermore, females are at a higher risk for developing autoimmune diseases. In this later context, it is interesting to note that a recent study showed that females had, on average, 1.7 times the frequency of self-specific T cells as males (7). Despite the fact that initial observations relating the sex of the individual with the immune response were made many years ago (8), little is known about the mechanisms underlying these differences.Some sex-specific variations in the immune response can be directly attributed to sex hormones (9). In humans, sex steroids can bind to intracellular receptors located in immune cells such as monocytes, B cells, and T cells and activate hormone-responsive genes, suggesting that they can directly affect sex-related differences in both innate and adaptive immune responses (10). Whereas estrogens are associated with inflammation and can stimulate proliferation and differentiation of lymphocytes and monocytes, androgens suppress the activity of immune cells by increasing the synthesis of anti-inflammatory cytokines (11, 12).To date, no clear associations have been found between biological and clinical differences in the immune response between males and females in humans. In one study, results from public gene expression data (13) showed that many of the genes induced by a yellow fever vaccine were preferentially activated in females (14). However, whether these differences correlate with poor antibody outcomes remains to be determined.In this study, we sought to determine whether we could identify biomarkers from peripheral blood that could explain the sex-related differences in the serological response to the trivalent inactivated seasonal influenza vaccine (TIV) in both young and older cohorts.Young and older females had higher neutralizing antibodies than age-matched males, consistent with previous reports (15). Females also showed higher expression of inflammatory markers. However, none of these specific sex-related differences correlated with the observed disparities in the antibody response to TIV. Nevertheless, using a machine learning approach, we identified a set of genes previously shown to be regulated by testosterone and participating in lipid biosynthesis, whose expression was negatively associated with antibody responses to TIV in the male subjects in our study. Moreover, males with high levels of serum testosterone and expressing related gene signatures in blood cells showed the lowest neutralizing responses to TIV. These results suggest that testosterone might be immunosuppressive in vivo in humans, and indicate that its effect on an influenza vaccine and other immune responses could be due to the regulation of genes implicated in the metabolism of lipids.     

Skeletal Histomorphometry in Subjects on Teriparatide or Zoledronic Acid Therapy (SHOTZ) Study: A Randomized Controlled Trial

Context: Recent studies on the mechanism of action (MOA) of bone-active drugs have rekindled interest in how to present and interpret dynamic histomorphometric parameters of bone remodeling. Objective: We compared the effects of an established anabolic agent, teriparatide (TPTD), with those of a prototypical antiresorptive agent, zoledronic acid (ZOL). Design: This was a 12-month, randomized, double-blind, active-comparator controlled, cross-sectional biopsy study. Setting: The study was conducted at 12 U.S. and Canadian centers. Subjects: Healthy postmenopausal women with osteoporosis participated in the study. Interventions: Subjects received TPTD 20 μg once daily by sc injection (n = 34) or ZOL 5 mg by iv infusion at baseline (n = 35). Main Outcome Measures: The primary end point was mineralizing surface/bone surface (MS/BS), a dynamic measure of bone formation, at month 6. A standard panel of dynamic and static histomorphometric indices was also assessed. When specimens with missing labels were encountered, several methods were used to calculate mineral apposition rate (MAR). Serum markers of bone turnover were also measured. Results: Among 58 subjects with evaluable biopsies (TPTD = 28; ZOL = 30), MS/BS was significantly higher in the TPTD group (median: 5.60 vs. 0.16%, P < 0.001). Other bone formation indices, including MAR, were also higher in the TPTD group (P < 0.05). TPTD significantly increased procollagen type 1 N-terminal propeptide (PINP) at months 1, 3, 6, and 12 and carboxyterminal cross-linking telopeptide of collagen type 1 (CTX) from months 3 to 12. ZOL significantly decreased PINP and CTX below baseline at all time points. Conclusions: TPTD and ZOL possess fundamentally different mechanisms of action with opposite effects on bone formation based on this analysis of both histomorphometric data and serum markers of bone formation and resorption. An important mechanistic difference was a substantially higher MS/BS in the TPTD group. Overall, these results define the dynamic histomorphometric characteristics of anabolic activity relative to antiresorptive activity after treatment with these two drugs.