Atezolizumab and bevacizumab-induced encephalitis in advanced hepatocellular carcinoma: Case report and literature review

Introduction:On the basis of the results of the IMBRAVE-150 trial, the combination of atezolizumab, a programmed cell death ligand 1 (PD-L1) antibody, as well as bevacizumab, a vascular endothelial growth factor (VEGF) antibody, represents a promising novel first-line therapy in patients with advanced hepatocellular carcinoma (HCC). Despite favorable safety data, serious adverse events have been described. However, central nervous system complications such as encephalitis have rarely been reported. We present the case of a 70-year-old woman with hepatitis C virus (HCV)-related liver cirrhosis and advanced HCC who developed severe encephalitis after only one cycle of atezolizumab/bevacizumab.Patient concerns:Ten days after administration, the patient presented with confusion, somnolence, and emesis. Within a few days, the patient''s condition deteriorated, and mechanical ventilation became necessary.Diagnosis:Cerebrospinal fluid (CSF) analysis showed increased cell count and elevated protein values. Further work-up revealed no signs of an infectious, paraneoplastic, or other autoimmune cause.Intervention:Suspecting an atezolizumab/bevacizumab-related encephalitis, we initiated a high-dose steroid pulse therapy as well as repeated plasmapheresis, which resulted in clinical improvement and remission of CSF abnormalities.Outcome:Despite successful weaning and transfer to a rehabilitation ward, the patient died of progressive liver cancer 76 days after initial treatment with atezolizumab/bevacizumab, showing no response.Conclusion:This case illustrates that rapid immunosuppressive treatment with prednisolone can result in remission even of severe encephalitis. We discuss this case in the context of available literature and previously reported cases of atezolizumab-induced encephalitis in different tumor entities, highlighting the diagnostic challenges in oncologic patients treated with immune checkpoint-inhibitors.     

Treating insomnia in Swiss primary care practices: A survey study based on case vignettes

Guidelines recommend cognitive behavioural therapy for insomnia (CBT‐I) as first‐line treatment for chronic insomnia, but it is not clear how many primary care physicians (PCPs) in Switzerland prescribe this treatment. We created a survey that asked PCPs how they would treat chronic insomnia and how much they knew about CBT‐I. The survey included two case vignettes that described patients with chronic insomnia, one with and one without comorbid depression. PCPs also answered general questions about treating chronic insomnia and about CBT‐I and CBT‐I providers. Of the 820 Swiss PCPs we invited, 395 (48%) completed the survey (mean age 54 years; 70% male); 87% of PCPs prescribed sleep hygiene and 65% phytopharmaceuticals for the patient who had only chronic insomnia; 95% prescribed antidepressants for the patient who had comorbid depression. In each case, 20% of PCPs prescribed benzodiazepines or benzodiazepine receptor agonists, 8% prescribed CBT‐I, 68% said they knew little about CBT‐I, and 78% did not know a CBT‐I provider. In the clinical case vignettes, most PCPs treated chronic insomnia with phytopharmaceuticals and sleep hygiene despite their lack of efficacy, but PCPs rarely prescribed CBT‐I, felt they knew little about it, and usually knew no CBT‐I providers. PCPs need more information about the benefits of CBT‐I and local CBT‐I providers and dedicated initiatives to implement CBT‐I in order to reduce the number of patients who are prescribed ineffective or potentially harmful medications.     

CELL RESPIRATION STUDIES : II. A COMPARATIVE STUDY OF THE OXYGEN CONSUMPTION OF BLOOD FROM NORMAL INDIVIDUALS AND PATIENTS WITH INCREASED LEUCOCYTE COUNTS (SEPSIS; CHRONIC MYELOGENOUS LEUCEMIA).

1. The oxygen consumption of blood of normal individuals, when the hemoglobin is saturated with oxygen, is practically zero within the limits of experimental error of the microspirometer used. 2. The oxygen consumed in a microspirometer by the blood of patients with chronic myelogenous leucemia with a high white blood cell count, and of one with leucocytosis from sepsis, was proportional to the number of adult polymorphonuclear neutrophils in the blood. 3. No correlation could be made between the rate of oxygen absorption and the total number of white blood cells in the blood, or the total number of immature cells, or the number of red blood cells, or the amount of oxyhemoglobin. 4. The blood of patients with chronic myelogenous leucemia continued to use oxygen in the microspirometer longer than that of normal individuals, and the hemoglobin, in the leucemic bloods, became desaturated even though exposed to air. 5. In blood in which the bulk. of the cells were immature and the mature cells few, the oxygen consumption was lower than in blood in which the mature cells predominated. The rate of oxygen consumption of the immature cells was relatively low as compared to the mature. 6. The slower rate of oxygen absorption by the immature leucocytes in chronic myelogenous leucemia as compared to the mature cells, places them, in accord with Warburg''s reports, in the class of the malignant tissues in this respect rather than in the group of young or embryonic cells.     

Spermatic cord liposarcomas incidentally found during hernia surgery: is histology of any lipoma mandatory? A review of the literature

Abstract

Purpose: Liposarcomas found incidentally during open or laparoscopic inguinal hernia surgery are extremely rare. It is unclear, whether any adipose tissue being removed during inguinal hernia surgery must be sent for histology due to the potential risk of liposarcoma of the spermatic cord. This study aims to evaluate the frequency of liposarcomas incidentally found in the inguinal canal during hernia surgery and tries to derive evidence-based recommendations regarding the optimal management of any fatty tissue found in the inguinal canal.

Methods: A literature review of the PubMed/Medline electronic databases between January 1980 and January 2019 was performed using the search terms ‘inguinal hernia’ and ‘liposarcoma’. There was only one study available on this topic. Therefore, an additional literature review was performed analyzing all reports on patients with incidentally detected liposarcomas of the spermatic cord in the inguinal canal during hernia surgery.

Results: There was only one retrospective study evaluating the frequency of inguinal liposarcoma found at hernia operations with a frequency of less than 0.1%. There were 18 cases of spermatic cord liposarcomas that were truly found incidentally during operation for an unsuspected symptomatic or incarcerated inguinal hernia. These included 16 case reports with a total of 18 patients and 19 liposarcomas. All patients were male with a median age of 62.5?years (range: 24–86?years) years. Median size of liposarcoma was 10.5?cm (range: 3–30?cm). In seven patients, the inguinal liposarcoma was an extension of a retroperitoneal sarcoma. Treatment consisted of radical orchidectomy during the primary operation in 12 patients. Three out of the seven patients with retroperitoneal extension of the tumor underwent a secondary operation with complete resection of the tumor.

Conclusions: Currently, there is no evidence-based recommendation available regarding the management of lipomas detected during open or laparoscopic inguinal hernia surgery. Due to the extremely low risk of the presence of a liposarcoma, routine histologic examination cannot be recommended unless the diameter exceeds 10?cm.     

Autophagy facilitates the release of immunogenic signals following chemotherapy in 3D models of mesothelioma

We have previously shown that nearly half of mesothelioma patients have tumors with low autophagy and that these patients have a significantly worse outcome than those with high autophagy. We hypothesized that autophagy may be beneficial by facilitating immunogenic cell death (ICD) of tumor cells following chemotherapy. An important hallmark of ICD is that death of tumor cells is preceded or accompanied by the release of damage‐associated molecular pattern molecules (DAMPs), which then can stimulate an antitumor immune response. Therefore, we measured how autophagy affected the release of three major DAMPs: high mobility group box 1 (HMGB1), ATP, and calreticulin following chemotherapy. We found that autophagy in three‐dimensional (3D) models with low autophagy at baseline could be upregulated with the cell‐permeant Tat‐BECN1 peptide and confirmed that autophagy in 3D models with high autophagy at baseline could be inhibited with MRT 68921 or ATG7 RNAi, as we have previously shown. In in vitro 3D spheroids, we found that, when autophagy was high or upregulated, DAMPs were released following chemotherapy; however, when autophagy was low or inhibited, DAMPs release was significantly impaired. Similarly, in ex vivo tumors, when autophagy was high or upregulated, HMGB1 was released following chemotherapy but, when autophagy was low, HMGB1 release was not seen. We conclude that autophagy can be upregulated in at least some tumors with low autophagy and that upregulation of autophagy can restore the release of DAMPs following chemotherapy. Autophagy may be necessary for ICD in this tumor.     

Effect of mate tea consumption on rapid force production after eccentric exercise: a randomized,controlled, crossover study

Sport Sciences for Health - Unusual eccentric exercise (EE) may affect muscle ability to produce rapid force. Previous study suggested that short-term mate tea (MT) consumption may enhance muscle...     

Preformed T cell alloimmunity and HLA eplet mismatch to guide immunosuppression minimization with tacrolimus monotherapy in kidney transplantation: Results of the CELLIMIN trial

Personalizing immunosuppression is a major objective in transplantation. Transplant recipients are heterogeneous regarding their immunological memory and primary alloimmune susceptibility. This biomarker-guided trial investigated whether in low immunological-risk kidney transplants without pretransplant DSA and donor-specific T cells assessed by a standardized IFN-γ ELISPOT, low immunosuppression (LI) with tacrolimus monotherapy would be non-inferior regarding 6-month BPAR than tacrolimus-based standard of care (SOC). Due to low recruitment rates, the trial was terminated when 167 patients were enrolled. ELISPOT negatives (E−) were randomized to LI (n = 48) or SOC (n = 53), E+ received the same SOC. Six- and 12-month BPAR rates were higher among LI than SOC/E− (4/35 [13%] vs. 1/43 [2%], p = .15 and 12/48 [25%] vs. 6/53 [11.3%], p = .073, respectively). E+ patients showed similarly high BPAR rates than LI at 6 and 12 months (12/55 [22%] and 13/66 [20%], respectively). These differences were stronger in per-protocol analyses. Post-hoc analysis revealed that poor class-II eplet matching, especially DQ, discriminated E− patients, notably E−/LI, developing BPAR (4/28 [14%] low risk vs. 8/20 [40%] high risk, p = .043). Eplet mismatch also predicted anti-class-I (p = .05) and anti-DQ (p < .001) de novo DSA. Adverse events were similar, but E−/LI developed fewer viral infections, particularly polyoma-virus-associated nephropathy (p = .021). Preformed T cell alloreactivity and HLA eplet mismatch assessment may refine current baseline immune-risk stratification and guide immunosuppression decision-making in kidney transplantation.