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Author(s):  
Andrea Scheffschick ◽  
Sina Fuchs ◽  
Vivianne Malmström ◽  
Iva Gunnarsson ◽  
Hanna Brauner

Abstract Systemic lupus erythematosus (SLE) is a multi-organ inflammatory disease with kidney inflammation, lupus nephritis (LN), being one of the most severe manifestations. Immune complex deposits, particularly in glomeruli, and T cells, B cells, and myeloid cells, mainly with extraglomerular localization, contribute to the inflammatory process. Natural killer (NK) cells have been suggested to play a role in autoimmune diseases, but have not been investigated in detail in renal lupus before. In this exploratory study, we performed the first characterization of NK cell number and distribution in LN kidney biopsies. Twelve SLE patients were analysed in the active phase of disease and five patients following immunosuppressive therapy. CD56 + cells, corresponding to NK cells or NKlike T cells, were identified in all patients, however, with reduced numbers in four out of five patients at follow up. Furthermore, cells were present in the kidney interstitium and peri-glomerular areas, but only rarely in glomeruli. Fluorescent co-staining of CD56 or NKp46 and CD3 revealed the presence of both CD56 +/NKp46 +CD3 -NK cells and CD56 +/NKp46 +CD3 +NK-like T cells. Compared to healthy kidney sections, one out of four LN patients showed increased numbers of NK cells. A correlation between CD56 + or NK cells with clinical parameters could not be observed, perhaps due to the small patient cohort. In conclusion, we have identified NK cells and NKlike T cells in LN kidney and performed the first detailed analysis of their localization during active and inactive disease. Their role in LN pathogenesis is, however, unclear and deserves further studies.


2021 ◽  
Vol 12 ◽  
Author(s):  
Sebastian Adeberg ◽  
Christina Sauer ◽  
Lena Lambert ◽  
Sebastian Regnery ◽  
Paul Windisch ◽  
...  

This single-center, single-arm trial investigates the feasibility of a psycho-oncological care program, which aims to reduce psychological distress and improve compliance with radiotherapy with mask fixation in patients with head and neck cancer or brain malignancies. The care program comprised (1) a screening/needs assessment and (2) the provision of a psycho-oncological intervention using imaginative stabilization techniques for distressed patients (distress due to anxiety ≥5) or in a case of subjective interest in the psycho-oncological intervention. Another allocation path to the intervention was directly through the radiation oncologist in charge who classified the patient as: in need of support to tolerate the immobilization device. Of a total of 1,020 screened patients, 257 (25.2%) patients indicated a distress ≥5 and 141 (13.8%) patients reported panic attacks. 25% of the patients reported a subjective interest in psycho-oncological support. A total of 35 patients received the psycho-oncological intervention, of which 74% were assigned by radiation oncologists. In this small patient cohort, no significant pre-post effects in terms of depression, anxiety, distress, and quality of life (mental and physical component scores) could be detected. Our results indicate a good feasibility (interdisciplinary workflow and cooperation, allocation by physicians in charge) of the psycho-oncological care program for this cohort of patients before radiotherapy with mask fixation. The screening results underline the high psychological distress and demand for psycho-oncological support. However, since the utilization of our intervention was low, future studies should reduce the barriers and improve compliance to psycho-oncological services by these patients.Clinical Trial Registration: https://www.drks.de/drks_web/setLocale_EN.do #DRKS00013493


Author(s):  
Katharina Kessel ◽  
Robert Seifert ◽  
Matthias Weckesser ◽  
Martin Boegemann ◽  
Sebastian Huss ◽  
...  

Abstract Introduction Fibroblast activation protein (FAP) has been recently presented as new imaging target for malignant diseases and offers high contrast to surrounding normal tissue. FAP tracer uptake has been reported in various tumor entities. The aim of this study was to compare FAP and Prostate-specific membrane antigen (PSMA) expression in primary prostate cancer employing histological analyses and PET imaging in two small patient collectives. Methods Two independent small patient collectives were included in this study. For cohort A, data of 5 prostate cancer patients and 3 patients with benign prostate hyperplasia were included. Patients with prostate cancer were initially referred for PSMA PET staging. Radical prostatectomy was performed in all patients and prostate specimen of patients and biopsies of healthy controls were available for further evaluation. Histological workup included HE and immunohistochemistry using PSMA Ab, FAP Ab. Cohort B consists of 6 Patients with diagnosed mCRPC and available PSMA as well as FAP PET. Results Patients with proven prostate cancer infiltration exhibited strong positivity for PSMA in both primary tumors and lymph node metastases while stainings for FAP were found positive in some cases, but not all (2/5). Controls with BPH presented moderate PSMA staining and in one case also with a positive FAP staining (1/3). PET imaging with FAP seemed to result in more precise results in case of low PSMA expression than PSMA-PET. Conclusions While PSMA staining intensity is a valid indicator of prostate cancer in both primary tumor and lymph node metastases, the expression of FAP seems to be heterogeneous but not necessarily linked to cancer-associated fibroblasts. It is also present in inflammation-associated myofibroblasts. Therefore, its ultimate role in prostate cancer diagnosis remains a subject of discussion.


2021 ◽  
Vol 37 (S1) ◽  
pp. 38-38
Author(s):  
Prachi Manchanda ◽  
Karen Mark ◽  
Judith Rubinstein

IntroductionThe National Institute of Health and Care Excellence (NICE) issued a supplementary advice in 2009 stating that treatments for patients with short life expectancies (<24 months) can exceed the cost-effectiveness threshold of GBP30,000 (EUR34,668) per additional quality-adjusted life-year (QALY), as long as the treatment is indicated for small patient populations and there is sufficient evidence that it extends life (≥ three months), compared with current National Health Service (NHS) treatments. This study investigated how often NICE reimburses treatments that meet end-of-life (EOL) criteria.MethodsHealth technology assessments (HTAs) conducted by NICE from 2009 to 2020 were reviewed for approved oncology drugs. Terminated appraisals were excluded. Data regarding EOL criteria in these submissions were then gathered. The HTA decisions were divided into the following categories: EOL criteria met; EOL criteria not met; and EOL criteria not applicable. A chi-square analysis was performed.ResultsA total of 316 reviews were assessed in the final sample, of which 71 percent (n = 223) of decisions were positive. Out of the positive decisions, 43 percent (n = 96), 25 percent (n = 55), and 32 percent (n = 72) of decisions were in the EOL criteria met, EOL criteria not met, and EOL criteria not applicable groups, respectively. The chi-square analysis showed a significant correlation between HTA decisions and EOL criteria (p = 0.0008). These results were consistent when the “EOL criteria not applicable” group was excluded (p = 0.001). When the analysis was performed between the “EOL criteria met” and “EOL criteria not met”, along with “EOL criteria not applicable” groups, it showed a possible correlation (p = 0.05).ConclusionsThis study showed that in oncology, NICE reimburses treatments that meet EOL criteria more often than treatments that attempt, but fail, to meet the EOL criteria.


2021 ◽  
Vol 10 (23) ◽  
pp. 5574
Author(s):  
Matthias P. Fabritius ◽  
Najib Ben Khaled ◽  
Wolfgang G. Kunz ◽  
Jens Ricke ◽  
Max Seidensticker

Intrahepatic cholangiocarcinoma is a highly aggressive malignancy with an increasing incidence in recent years. Prognosis is poor and most patients are not eligible for resection at the time of initial diagnosis due to the anatomic location, inadequate hepatic reserve, limiting comorbidities or metastatic disease. Several locoregional therapies from the field of interventional radiology exist for patients who are not amenable for surgery, or in case of local recurrence as a single treatment modality or combined with systemic treatment. To date, evidence is limited, with most conclusions drawn from single-center studies with small patient cohorts, often treated in the salvage situation or for local recurrence after initial resection. Nevertheless, the results are promising and suggest a survival benefit in selected patients. This narrative review focuses on the use of different locoregional treatment options for intrahepatic cholangiocarcinoma.


Toxins ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 800
Author(s):  
Sarah N. C. Gimenes ◽  
Jacqueline A. G. Sachett ◽  
Mônica Colombini ◽  
Luciana A. Freitas-de-Sousa ◽  
Hiochelson N. S. Ibiapina ◽  
...  

In the Brazilian Amazon, Bothrops atrox snakebites are frequent, and patients develop tissue damage with blisters sometimes observed in the proximity of the wound. Antivenoms do not seem to impact blister formation, raising questions regarding the mechanisms underlying blister formation. Here, we launched a clinical and laboratory-based study including five patients who followed and were treated by the standard clinical protocols. Blister fluids were collected for proteomic analyses and molecular assessment of the presence of venom and antivenom. Although this was a small patient sample, there appeared to be a correlation between the time of blister appearance (shorter) and the amount of venom present in the serum (higher). Of particular interest was the biochemical identification of both venom and antivenom in all blister fluids. From the proteomic analysis of the blister fluids, all were observed to be a rich source of damage-associated molecular patterns (DAMPs), immunomodulators, and matrix metalloproteinase-9 (MMP-9), suggesting that the mechanisms by which blisters are formed includes the toxins very early in envenomation and continue even after antivenom treatment, due to the pro-inflammatory molecules generated by the toxins in the first moments after envenomings, indicating the need for local treatments with anti-inflammatory drugs plus toxin inhibitors to prevent the severity of the wounds.


Author(s):  
Tommy Le ◽  
Eunice Chun ◽  
Ivan Lopez ◽  
Karl Kingsley ◽  
Linh Nguyen

Introduction: The human digestive tract is composed of an immense variety of microorganisms, which have been linked to many health problems such as obesity. There are many studies that demonstrate the association of cariogenic pathogens in dental patients and overall health. Selenomonas noxia, a gram negative anaerobe that is unable to metabolize sucrose and Akkermansia muciniphila, a gram negative anaerobe known to metabolize fats are two examples of pathogens that play a role in overall health.  Objectives: Few studies have investigated both Selenomonas noxia (SN) and Akkermansia muciniphila (AM) with the same patient samples. The objective of this study was to analyze and evaluate the prevalence of both these organisms in a dental school-based setting.  Methods: Saliva was collected from pediatric patients using an IRB-approved protocol. DNA was isolated for PCR screening and quality tested using the nanodrop. Gel electrophoresis was used for visualization. Forty seven (n=47) patients ranging from five to fifteen years of age (average 10.3) were screened. Nearly two-thirds of patients were male (64.6%) with the vast majority identified as Hispanic (72.9%) or other minority (25.0%)  Results: DNA was successfully isolated with an overall average DNA concentration of 1.43 ug/uL and overall purity (A260:A80 ratio) of 1.88. Of the forty seven patients, four patients were positive for SN. There was no presence of AM in the samples. Conclusions: Research regarding AM and SN may suggest they inhabit different niches in the microbial community. The preliminary data of this pilot study suggests that SN could be found in pediatric patients while AM is not likely prevalent. However, due to the small patient sample size and large differences observed from these samples further research and analysis would need to be conducted to validate the findings.


2021 ◽  
Vol 11 (9) ◽  
pp. 440-448
Author(s):  
Piotr Jaworski

The physiotherapy process in children is specific and requires much more patience and understanding than in adults. Working with a child is not only related to the physiotherapy of a small patient, but also in a very good cooperation between the parent-physiotherapist. The paper presents selected issues of children's therapy in the light of research papers published in renowned scientific journals dealing with medical issues.


2021 ◽  
Vol 108 (Supplement_6) ◽  
Author(s):  
C Vincenti ◽  
V Bhattacharya ◽  
N Kansal

Abstract Aim Limb amputations have many post-op complications, including pain. The evidence supporting the use of nerve sheath catheters (NSC) to manage post-op pain is mixed. Current literature suggests NSC reduces post-op opioid requirements but does not reduce pain score, phantom limb pain or chronic stump pain. This study compared post-op pain in those with and without NSC after above knee amputations (AKA) and below knee amputations (BKA). Method Retrospective data from April 2014 – March 2017 was reviewed. Information regarding indication, anaesthetic, morphine requirement at 72 hours, phantom limb, chronic limb pain and a pain scale (1-10) at 24, 48 and 72 hours were collected. Results 32 patients were involved in the study. 11 had NSC for pain control. Of those patients without NSC, 43% experienced no pain. In comparison, 33% of those with NSC experienced no post-op pain. Phantom limb pain was experienced in a higher proportion of patients with NSC (18%) and in those with AKA (11%). 18% of patients with NSC experienced chronic limb pain, compared to 33% without NSC. 62% of patients with NSC required morphine at 72 hours and at higher dosages compared to those without. However, two patients used large amounts of morphine potentially giving spurious results. Conclusions Though limited by small patient group, patients with NSC were more likely to require morphine at 72 hours and at higher dosages but were less likely to experience chronic limb pain thus proving the role of NSC in post-op pain control.


2021 ◽  
Vol 3 ◽  
pp. 19
Author(s):  
Ayodele Sasegbon ◽  
Ulrike Hammerbeck ◽  
Emilia Michou ◽  
Ivy Cheng ◽  
Mengqing Zhang ◽  
...  

Introduction: Dysphagia often occurs during Parkinson’s disease (PD) and can have severe consequences. Recently, neuromodulatory techniques have been used to treat neurogenic dysphagia. Here we aimed to compare the neurophysiological and swallowing effects of three different types of neurostimulation, 5 Hertz (Hz) repetitive transcranial magnetic stimulation (rTMS), 1 Hz rTMS and pharyngeal electrical stimulation (PES).   Method: 12 PD patients with dysphagia were randomised to receive either 5 Hz rTMS, 1 Hz rTMS, or PES. In a cross-over design, patients were assigned to one intervention and received both real and sham stimulation. Patients received a baseline videofluoroscopic (VFS) assessment of their swallowing, enabling penetration aspiration scores (PAs) to be calculated for: thin fluids, paste, solids and cup drinking. Swallowing timing measurements were also performed on thin fluid swallows only. They then had baseline recordings of motor evoked potentials (MEPs) from both pharyngeal and (as a control) abductor pollicis brevis (APB) cortical areas using single-pulse TMS. Subsequently, the intervention was administered and post interventional TMS recordings were taken at 0 and 30 minutes followed by a repeat VFS within 60 minutes of intervention. Results: All interventions were well tolerated. Due to lower than expected recruitment, statistical analysis of the data was not undertaken. However, with respect to PAs swallowing timings and MEP amplitudes, there was visual separation in a positive direction between active and sham groups for all interventions. Conclusion: PES, 5 Hz rTMS and 1 Hz rTMS are tolerable interventions in PD related dysphagia. Due to small patient numbers no definitive conclusions could be drawn from the data with respect to individual interventions improving swallowing function and comparative effectiveness between interventions. Larger future studies are needed to further explore the efficacy of these neuromodulatory treatments in Parkinson’s Disease associated dysphagia.


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