Cancer- and cardiac-induced cachexia: same fate through different inflammatory mediators?

Background

Inflammation is widely recognized as the driving force of cachexia induced by chronic diseases; however, therapies targeting inflammation do not always reverse cachexia. Thus, whether inflammation per se plays an important role in the clinical course of cachectic patients is still a matter of debate.

Aims

To give new insights into cachexia’s pathogenesis and diagnosis, we performed a comprehensive literature search on the contribution of inflammatory markers to this syndrome, focusing on the noncommunicable diseases cancer and cardiovascular diseases.

Methods

A systematic review was performed in PubMed using the keywords (“cancer” OR “cardiac” cachexia AND “human” OR “patient” AND “plasma” or “serum”). A total of 744 studies were retrieved and, from these, 206 were selected for full-text screening. In the end, 98 papers focusing on circulating biomarkers of cachexia were identified, which resulted in a list of 113 different mediators.

Results

Data collected from the literature highlight the contribution of interleukin-6 (IL-6) and C-reactive protein (CRP) to cachexia, independently of the underlying condition. Despite not being specific, once the diagnosis of cachexia is established, CRP might help to monitor the effectiveness of anti-cachexia therapies. In cardiac diseases, B-type natriuretic peptide (BNP), renin, and obestatin might be putative markers of body wasting, whereas in cancer, growth differentiation factor (GDF) 15, transforming growth factor (TGF)-β1 and vascular endothelial growth factor (VEGF) C seem to be better markers of this syndrome. Independently of the circulating mediators, NF-κB and JAK/STAT signaling pathways play a key role in bridging inflammation with muscle wasting; however, therapies targeting these pathways were not proven effective for all cachectic patients.

Conclusion

The critical and integrative analysis performed herein will certainly feed future research focused on the better comprehension of cachexia pathogenesis toward the improvement of its diagnosis and the development of personalized therapies targeting specific cachexia phenotypes.

     

Expansion of plasmablasts and loss of memory B cells in peripheral blood from COVID-19 patients with pneumonia

Studies on the interactions between SARS-CoV-2 and humoral immunity are fundamental to elaborate effective therapies including vaccines. We used polychromatic flow cytometry, coupled with unsupervised data analysis and principal component analysis (PCA), to interrogate B cells in untreated patients with COVID-19 pneumonia. COVID-19 patients displayed normal plasma levels of the main immunoglobulin classes, of antibodies against common antigens or against antigens present in common vaccines. However, we found a decreased number of total and naïve B cells, along with decreased percentages and numbers of memory switched and unswitched B cells. On the contrary, IgM⁺ and IgM⁻ plasmablasts were significantly increased. In vitro cell activation revealed that B lymphocytes showed a normal proliferation index and number of dividing cells per cycle. PCA indicated that B-cell number, naive and memory B cells but not plasmablasts clustered with patients who were discharged, while plasma IgM level, C-reactive protein, D-dimer, and SOFA score with those who died. In patients with pneumonia, the derangement of the B-cell compartment could be one of the causes of the immunological failure to control SARS-Cov2, have a relevant influence on several pathways, organs and systems, and must be considered to develop vaccine strategies.     

Substance use and perceived symptom improvement among patients with bipolar disorder and substance dependence

BACKGROUND: Bipolar disorder (BPD) is the Axis I disorder with the highest risk for coexisting substance use disorder. One explanation for this phenomenon is the 'self-medication hypothesis', which states that some patients experience improvement in psychiatric symptoms as a result of substance use. We thus investigated reasons for substance use and perceived substance-induced improvement in BPD symptoms among patients with current BPD and substance dependence. METHODS: A total of 45 patients received six monthly assessments; 21 also received integrated group therapy (IGT), focusing simultaneously on BPD and substance dependence, while 24 did not receive IGT. Patients reported at intake their current reasons for initiating substance use (including BPD symptoms) and the effects of substance use on those symptoms. RESULTS: Nearly all patients initiated substance use because of at least one BPD symptom, especially depression (77.8%) and racing thoughts (57.8%); most (66.7%) reported improvement in at least one BPD symptom as a result of substance use. Among patients reporting substance-induced improvement in BPD symptoms, those receiving IGT reported fewer days of drug use over the 6-month study period than those not receiving IGT; this difference was not significant among patients without substance-induced improvement in BPD symptoms. LIMITATIONS: The study is limited by its small sample size and by the potential inaccuracy of self-reports regarding the effects of substance use on mood. CONCLUSIONS: Substance dependent patients who report that substance use improves their BPD symptoms may benefit from treatment that focuses simultaneously on both disorders.     

Activities of Murine Peripheral Blood Lymphocytes Provide Immune Correlates That Predict Francisella tularensis Vaccine Efficacy

We previously identified potential correlates of vaccine-induced protection against Francisella tularensis using murine splenocytes and further demonstrated that the relative levels of gene expression varied significantly between tissues. In contrast to splenocytes, peripheral blood leukocytes (PBLs) represent a means to bridge vaccine efficacy in animal models to that in humans. Here we take advantage of this easily accessible source of immune cells to investigate cell-mediated immune responses against tularemia, whose sporadic incidence makes clinical trials of vaccines difficult. Using PBLs from mice vaccinated with F. tularensis Live Vaccine Strain (LVS) and related attenuated strains, we combined the control of in vitroFrancisella replication within macrophages with gene expression analyses. The in vitro functions of PBLs, particularly the control of intramacrophage LVS replication, reflected the hierarchy of in vivo protection conferred by LVS-derived vaccines. Moreover, several genes previously identified by the evaluation of splenocytes were also found to be differentially expressed in immune PBLs. In addition, more extensive screening identified additional potential correlates of protection. Finally, expression of selected genes in mouse PBLs obtained shortly after vaccination, without ex vivo restimulation, was different among vaccine groups, suggesting a potential tool to monitor efficacious vaccine-induced immune responses against F. tularensis. Our studies demonstrate that murine PBLs can be used productively to identify potential correlates of protection against F. tularensis and to expand and refine a comprehensive set of protective correlates.     

Presence of repeating hyperostotic bones in dorsal pterygiophores of the oarfish,Regalecus russellii

Hyperostosis, excessive bone growth along bone that stems from bone, periosteum or articular or epiphyseal cartilage, occurs in at least 22 families of fishes most of which are tropical or subtropical marine species. While the presence of hyperostosis is well documented in fishes, the mechanism driving the development of the excessive bone growth is unclear. This study documented hyperostosis along the dorsal pterygiophores in both sexes of oarfish, Regalecus russellii; however, it was not present in all specimens examined. This is the second lampridiform fish with hyperostoses and the first case documented in a deeper‐water, epi‐mesopelagic fish. In oarfish, the majority of the dorsal pterygiophores tissues are poorly mineralized, anosteocytic bones with some fish displaying localized stiffened, hyperostotic growths near the distal edge. Oarfish lack a swim bladder so they must continuously beat their bi‐directional dorsal fin to maintain position within the water column while engaged in locomotory behavior. These fishes have areas of localized, hyperostotic skeletal elements along the dorsal pterygiophores that, presumably, function as a stiffened lever system to support fin undulation. It was noted that hyperossification was not present in all fish examined and was only documented in fish with total lengths greater than 3 m.     

The estimation of premorbid intelligence levels among Portuguese speakers: the Irregular Word Reading Test (TeLPI)

Information regarding cognitive abilities in earlier stages of life is essential to ascertain if and to what extent these may have declined. When unavailable, clinicians rely on estimate methods. One of the contemporary methods used worldwide combines performance on irregular word reading test with demographics since it has shown to provide reliable estimates of premorbid ability. Hence, a reading test portuguese irregular word reading test (TeLPI) was developed, filling an important gap in the neuropsychological evaluation of Portuguese speakers. Using 46 irregular, infrequent Portuguese words, TeLPI was validated against Wechsler Adult Intelligence Scale (WAIS)-III (N = 124), and regression-based equations were determined to estimate premorbid IQ considering TeLPI scores and demographic variables. TeLPI scores accounted for 63% of the variance of WAIS-III Full-Scale IQ, 62% of Verbal IQ, and 47% of Performance IQ and thus were considered valid for premorbid intelligence estimation.     

PCR study of a series of ASCUS cases HPV-positive by HCII

Most guidelines currently recommend the testing of human papillomavirus (HPV) in ASCUS cases. The most used method for this purpose is Hybrid Capture II (HCII), but PCR techniques with GP5+/6+ primers can be also applied. Furthermore, the HCII high‐risk probe test for detection of HPV shows cross‐reactivity with low‐risk HPV. Although this cross‐reactivity has been studied in screening populations, it has received little attention in ASCUS cases. To compare the performance of the HCII high‐risk probe test and PCR for the detection of HPV in ASCUS cases. We randomly selected 83 ASCUS cases that were positive for high‐risk HPV by HCII and applied the PCR test using MYO9‐11 and GP5+/6+ primers to samples from these cases. Our results show cross‐reactivity with low‐risk HPV in 25.3% (21/83) of the HCII+ PCR+ cases. Regarding the follow‐up our results emphasize the importance of HPV typing, especially for HPV 16 infection. We propose the use of PCR techniques using GP5+/6+ consensus primers for the screening of HPV in ASCUS. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.     

Fine-needle aspiration biopsy of breast adenomyoepithelioma: A potential false positive pitfall and presence of intranuclear cytoplasmic inclusions

Cytologic diagnosis of adenomyoepithelioma can be very challenging. We report fine needle aspiration cytology (FNAC) findings of a benign adenomyoepithelioma. The cytologic features are characterized by hypercellularity and the presence of numerous atypical dispersed cells with epithelioid morphology and intact cytoplasm. The nuclei showed stippled chromatin, irregular nuclear membrane, and prominent eosinophilic nucleoli. No necrosis or mitoses were seen. The presence of naked nuclei, and extensive intranuclear cytoplasmic inclusions were identified and raised the possibility of adenomyoepithelioma. Immunohistochemically, the atypical cells showed strong positivity for myosin heavy chain, p63, and CK5/6, while the epithelial cells reacted with estrogen receptors. This immunophenotypic pattern supports the myoepithelial origin of the atypical cell proliferation and favors the diagnosis of benign adenomyoepithelioma. However, biopsy was recommended to exclude malignancy. Histologically, the tumor showed prominent myoepithelial cells with significant atypia, intranuclear cytoplasmic inclusions, and dense cytoplasm. No evidence of malignancy was identified. In conclusion, we report a case of adenomyoepithelioma with a significant cytological atypia that may result in confusion with malignant breast tumors. The presence of intranuclear cytoplasmic inclusions, naked nuclei, and expression of myoepithelial markers should provide clues to the right diagnosis and benign nature of this lesion. Cytopathologists should be familiarized with this entity to avoid a misdiagnosis of carcinoma. Diagn. Cytopathol. 2012. © 2011 Wiley Periodicals, Inc.