The clinical efficacy and safety of single-agent pembrolizumab in patients with recurrent granulosa cell tumors of the ovary: a case series from a phase II basket trial

xlomafota.13 shared this article with you from Inoreader The clinical efficacy and safety of single-agent pembrolizumab in patients with recurrent granulosa cell tumors of the ovary: a case series from a phase II basket trial Via Latest Results for Investigational New Drugs Summary Background Treatment of recurrent, unresectable granulosa cell tumor (GCT) of the ovary can be challenging. Given the rarity of the tumor, alternative therapies have been difficult to evaluate in large prospective clinical trials. Currently, to our knowledge, there are no reports of the use of immune checkpoint inhibitors in GCT patients. Here, we present a case series of GCT patients treated with pembrolizumab who were enrolled in a phase II basket trial in advanced, rare solid tumors (ClinicalTrials.gov: NCT02721732). Cases We identified 5 patients with recurrent GCT (4 adult and 1 juvenile type); they had an extensive history of systemic therapy at study enrollment (range, 3–10), with most regimens resulting in less than 12 months of disease control. Pembrolizumab was administered in these patients, as per trial protocol. Although there were no objective responses according to the irRECIST guidelines, 2 patients with adult-type GCT exp erienced disease control for ≥ 12 months (565 and 453 days). In one, pembrolizumab represented the longest duration of disease control compared to prior lines of systemic therapy (565 days vs. 13 months). In the other, pembrolizumab was the second longest systemic therapy associated with disease control (453 days vs. 22 months) compared to prior lines of therapy. In this patient, pembrolizumab was discontinued following withdrawal of consent. PD-L1 expression was not observed in any baseline tumor samples. Pembrolizumab was well tolerated, with no grade 3 or 4 treatment-related adverse events. Conclusions Although our results do not support the routine use of pembrolizumab monotherapy in unselected GCT patients, some patients with adult-type GCT may derive a clinical benefit, with a low risk of toxicity. Future studies should investigate the role of immunotherapy and predictors of clinical benefit in this patient population. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Mesenteric Venous Thrombosis Due to Coronavirus

xlomafota.13 shared this article with you from Inoreader Mesenteric Venous Thrombosis Due to Coronavirus in a Post Roux-en-Y Gastric Bypass Patient: a Case Report Via Latest Results for Obesity Surgery View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Lymphatic filariasis

xlomafota.13 shared this article with you from Inoreader Lymphatic filariasis in Asia: a systematic review and meta-analysis Via Latest Results for Parasitology Research Abstract Lymphatic filariasis (LF) is an important neglected parasitic disease according to the World Health Organization. In this study, we aimed to determine the prevalence of human LF in Asia using a systematic review and meta-analysis approach. Records from 1990 to 2018 in reputable databases including PubMed, Science Direct, Embase, and Cochrane Library were searched using a panel of related keywords. All 48 countries of Asia were searched one by one in combination with the keywords. In all, 41,742 cases identified in this study were included in the analysis. According to our findings, the pooled prevalence of LF in Asia was estimated at 3% (95% CI: [1.7, 5.2]). There was no major trend in the cumulative prevalence of LF over time. Some countries in Asia including China, Japan, Vietnam, and South Korea succeeded in eliminating LF as a public health problem, but others still need to monitor the disease. Based on the initiative of the WHO starting in 2000, some co untries in Asia succeeded in eliminating LF as a public health problem. Other countries have taken steps to eliminate the disease with variable degrees of success. These efforts might be affected by issues such as climate change. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Regulation of human THP-1 macrophage polarization by Trichinella spiralis

xlomafota.13 shared this article with you from Inoreader Regulation of human THP-1 macrophage polarization by Trichinella spiralis Via Latest Results for Parasitology Research Abstract Trichinella spiralis is a foodborne zoonotic nematode, which causes trichinellosis. During the infection, parasite evades the host immune responses by direct and indirect (through excretory-secretory products) contact with host immune cells. One of the main targets for immunomodulation induced by helminths are macrophages. In this study, we examined whether direct contact of different stages of T. spiralis can affect the polarization of human THP-1 macrophages. Co-culture of adult parasite stage and cells in direct contact without LPS addition had a significant impact on TNFα levels. Interestingly, in settings with the addition of LPS, the levels of IL-1β and TNFα significantly increased in adult parasite and newborn larvae (NBL) but not for muscle larvae (ML). While we tested muscle larvae ESP products to compare its effect with whole ML parasite, we detect an increase of pro-inflammatory cytokines like IL-1β and TNFα in no LPS conditions. Whereas, muscle larvae ESP significantly suppressed the inflammatory response measured by IL-1β, TNFα, and IL-6 levels and anti-inflammatory IL-10 compared to LPS control. Our findings indicate the anti-inflammatory potential of T. spiralis muscle larvae excretory-secretory products and propose signaling pathways which might be engaged in the mechanism of how muscle larvae ESP affect human macrophages. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

PCR-based diagnosis is not always useful in the acute acquired toxoplasmosis in immunocompetent individuals

xlomafota.13 shared this article with you from Inoreader PCR-based diagnosis is not always useful in the acute acquired toxoplasmosis in immunocompetent individuals Via Latest Results for Parasitology Research Abstract Toxoplasmosis is the most prevalent zoonosis in the world and is associated with a large spectrum of diseases. Acute acquired toxoplasmosis (AAT) is considered a benign and self-limiting disease but severe postnatal infections have been reported, particularly in South America. Laboratory diagnosis is based on the detection of anti–Toxoplasma gondii IgM, IgG, and presence of low IgG avidity. However, these assays present limitations, and therefore, PCR has been suggested as an alternative diagnostic tool. In this study, we performed real-time and nested PCR in DNA blood samples from 59 individuals with AAT lasting less than 80 days. None of the patients had parasitic DNA detected by PCR, even in the more severe cases or when blood was collected early after disease onset. These negative results indicate that the parasitemia kinetics needs investigation to determine the best time for blood sampling, especially in immunocompetent individuals. Thus, we emphasize that a negative PCR result does not exclude recent T. gondii infection, and serological criteria are still decisive for the laboratory diagnosis of AAT. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Characterization and localization of antigens for serodiagnosis of human paragonimiasis

xlomafota.13 shared this article with you from Inoreader Characterization and localization of antigens for serodiagnosis of human paragonimiasis Via Latest Results for Parasitology Research Abstract Paragonimiasis is a foodborne trematode infection that affects 23 million people, mainly in Asia. Lung fluke infections lead frequently to chronic cough with fever and hemoptysis, and are often confused with lung cancer or tuberculosis. Paragonimiasis can be efficiently treated with praziquantel, but diagnosis is often delayed, and patients are frequently treated for other conditions. To improve diagnosis, we selected five Paragonimus kellicotti proteins based on transcriptional abundance, recognition by patient sera, and conservation among trematodes and expressed them as His-fusion proteins in Escherichia coli. Sequences for these proteins have 76–99% identity with amino acid sequences for orthologs in the genomes of Paragonimus westermani, Paragonimus heterotremus, and Paragonimus miyazakii. Immunohistology studies showed that antibodies raised to four recombinant proteins bound to the tegument of adult P. kel licotti worms, at the parasite host interface. Only a known egg antigen was absent from the tegument but present in developing and mature eggs. We evaluated the diagnostic potential of these antigens by Western blot with sera from patients with paragonimiasis (from MO and the Philippines), fascioliasis, and schistosomiasis, and with sera from healthy North American controls. Two recombinant proteins (a cysteine protease and a myoglobin) showed the highest sensitivity and specificity as diagnostic antigens, and they detected antibodies in sera from paragonimiasis patients with early or mature infections. In contrast, antibodies to egg yolk ferritin appeared to be specific marker for patients with adult fluke infections that produce eggs. Our study has identified and localized antigens that are promising for serodiagnosis of human paragonimiasis. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Periorbital human dirofilariasis

xlomafota.13 shared this article with you from Inoreader The first case of periorbital human dirofilariasis in the Czech Republic Via Latest Results for Parasitology Research Abstract Dirofilaria repens and Dirofilaria immitis are the most common filarial species affecting humans in Europe. Dirofilaria repens causes subcutaneous or ocular infection, whereas D. immitis is responsible mainly for the pulmonary form. In this report, we present the first human case of periorbital dirofilariasis in the Czech Republic. A 58-year-old woman suffered from an eyelid oedema, redness and pain in the left eye. After excising the parasite from her eyelid, all clinical symptoms disappeared. Based on the morphology and cytochrome oxidase I sequencing, the parasite was identified as D. repens. Histology revealed that the excised worm was female with absent microfilariae in uteri. With respect to the length of the incubation period and the sequence identity with a known Czech isolate, we concluded that D. repens was most likely of autochthonous origin. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

How I do it: Management of venous bleeding from the superior petrosal vein during endoscopic microvascular decompression

xlomafota.13 shared this article with you from Inoreader How I do it: Management of venous bleeding from the superior petrosal vein during endoscopic microvascular decompression Via Latest Results for Acta Neurochirurgica Abstract Background A repair strategy for venous bleeding from the superior petrosal vein (SPV) is essential during endoscopic microvascular decompression. Method Sliced oxycellulose seats are rounded off, making balls around 10 mm in diameter. When venous bleeding arises from the SPV, the first oxycellulose ball is placed just behind the SPV in the surgical view. A second ball is then applied in front of the SPV. The SPV is thus immediately and entirely covered by oxycellulose, and hemostasis is safely achieved with the preservation of the SPV. Conclusion This oxycellulose ball technique offers simple, reliable control of venous bleeding from the SPV. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Familial tendency in patients with lipoma of the filum terminale

xlomafota.13 shared this article with you from Inoreader Familial tendency in patients with lipoma of the filum terminale Via Latest Results for Child's Nervous System Abstract Purpose Lipoma of the filum terminale (FL) is an abnormality in which fat is deposited in the filum terminale. This lipoma is often detected by skin abnormalities in the lumbosacral area such as a sacrococcygeal dimple. Some cases may develop tethered cord and become symptomatic. However, the genetic basis of FL is still unclear. Methods This study aimed to determine whether there was a family history of FL or other forms of spina bifida among 54 families of 56 patients with FL and to examine whether there is a familial predisposition in FL. In addition, sex, age at diagnosis, presence of symptoms, presence of sacrococcygeal dimple, and the level of conus medullaris between familial and spontaneous cases were evaluated. Results Of the 54 families of FL patients, there were 48 siblings. Among the 48 siblings, 2 had "occult" FL. The frequency of FL among siblings was estimated to be 4.2% (2/48), which was significantly higher than the sum of previously reported cases of spontaneous FL (0.91%; p = 0.017). However, there was no significant difference in sex, age at diagnosis, presence of symptoms, presence of sacrococcygeal dimple, diameter of filum terminale, or level of conus medullaris between familial and spontaneous cases. Conclusion To our knowledge, this is the first report on familial FL and examination of the frequency of FL among siblings. The high probability of FL among siblings of FL patients suggests that genetic factors may play a role in FL development. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Wip1 Aggravates the Cerulein-Induced Cell Autophagy and Inflammatory Injury by Targeting STING/TBK1/IRF3 in Acute Pancreatitis

xlomafota.13 shared this article with you from Inoreader Wip1 Aggravates the Cerulein-Induced Cell Autophagy and Inflammatory Injury by Targeting STING/TBK1/IRF3 in Acute Pancreatitis Via Latest Results for Inflammation Abstract Acute pancreatitis (AP) is an inflammatory reaction of pancreatic tissue self-digestion, edema, hemorrhage, and even necrosis after the activation of pancreatic enzymes in the pancreas caused by a variety of etiologies. This study was aimed to explore the functions and mechanism of Wip1 in AP. Twenty male SD rats were randomly assigned into 2 groups (control group: saline treatment; AP group: cerulein treatment). And cerulein-treated AR42J cells were conducted as AP model in vitro. The levels of amylase were detected by using the Beckman biochemical analyzer. The levels of IFNβ and TNFα were analyzed by ELISA. The autophagosomes were observed by transmission electron microscopy. The Wip1-specific shRNAs were transfected to AR42J cells to silence the expression of Wip1. The levels of Wip1 were measured by qRT-PCR and Western blot. The levels of STING/TBK1/IRF3 and LC3 were measured by Western blot. The AP model was successfully constructed by cerulein a dministration. Wip1 was notably upregulated in AP models. Autophagy and STING pathway activation were involved in the development of AP. Wip1 inhibition counteracts the promotion effect on inflammatory response induced by cerulein in AR42J Cells. Wip1 inhibition inhibited the activity of the STING/TBK1/IRF3 and reduced LC3 levels in AP. This study preliminarily explored that Wip1 could regulate autophagy and participate in the development of AP through the STING/TBK1/IRF3 signaling pathway. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Decreased expression of TRIM3 gene predicts a poor prognosis in gastric cancer

xlomafota.13 shared this article with you from Inoreader Decreased expression of TRIM3 gene predicts a poor prognosis in gastric cancer Via Latest Results for Journal of Gastrointestinal Cancer Abstract Background/aims Tripartite motif-containing 3 (TRIM3) is a member of the TRIM protein family which is known to be involved in development of numerous tumor types. However, the prognostic role of TRIM3 in gastric cancer (GC) remained to be clarified. The aim of this study was to evaluate the expression pattern and prognostic significance of TRIM3 gene and its relationship with β-catenin, CyclinD, and BCL2 expression in patients with GC. Methods A total of 40 fresh primary gastric cancer tumors and their matched adjacent noncancerous tissues were selected from the First Affiliated Hospital of Mashhad University. Real-time quantitative RT-PCR was performed to evaluate differences in TRIM3 expression in GC and normal tissues. The correlation between TRIM3 expression level and patients' overall survival, some clinicopathological variables, and β-catenin, CyclinD, and BCL-2 genes expression level were also studied. Moreover, patients were divided in two groups according to the TRIM3 expression levels: low and high. Results Compared to noncancerous tissues, TRIM3 expression in GC tissues was significantly increased (fold change = 1.58). Kaplan–Meier survival analysis revealed a significant difference of patient survival according to TRIM3 expression status (P = 0.012). Low TRIM3 expression was associated with shorter overall survival and was an independent predictor for poor prognosis in GC patients (HR, 1.25; 95%CI, 1.02-1.60; P = 0.045). Expression of TRIM3 was negatively correlated with expression of β-catenin, BCL-2, and CyclinD as genes for proliferation, apoptosis, and the cell cycle in GC patients. Conclusions This study demonstrates that decreased level of TRIM3 mRNA expression is associated with poor prognosis in patients with gastric cancer. TRIM3 may play a protective role in gastric cancer by relieving the effects of cancer progressive genes and could be considered for further investigations as a prognostic biomarker. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Safety and tolerability of regorafenib:

xlomafota.13 shared this article with you from Inoreader Safety and tolerability of regorafenib: a real-life experience Via Latest Results for Journal of Gastrointestinal Cancer Abstract Background Regorafenib has been approved among the treatment options for patients with advanced stage colorectal cancer (CRC), hepatocellular carcinoma (HCC), and gastrointestinal stromal tumors (GIST). In this study, we aim to report the real-life experience of the safety and tolerability regorafenib in our institution. Methods We conducted a retrospective chart review of 43 patients who received regorafenib in Kuwait Cancer Control Center (KCCC) from 2016 to the end of 2019. Data collected include diagnosis, patient demographics, performance status, number of previous lines of treatment, number of treatment cycles, side effects, best-tolerated dose, and treatment discontinuation due to intolerability. Univariate analysis with Pearson chi-square test were conducted to study co-relation between discontinuation rates and several factors. Results We had available data for 43 patients (23 males and 20 females). Of the patients, 83.7% had an ECOG performance status of 0 or 1. Seventy-three percent were diagnosed with metastatic CRC, 21% were diagnosed with HCC and 6% were diagnosed with GIST tumors. Half of the patients received 3 lines or more of treatment prior to regorafenib. The median number of cycles received was 3.7 with 11.6% of patients still on active treatment at the time of analysis. The most reported grade 3 and above side effects included rash (41.9%), fatigue (39.6 %), hypertension (25.6%), mucositis (21.9%), hand-foot syndrome (2.3%), and hyperbilirubinemia (4.6%). The best-tolerated dose was 80 mg and that was achieved in 44.2% of patients. The recommended dose of 160 mg could only be achieved in 20.9% of patients. The treatment was discontinued because of intolerability in 25.6% of patients. The discontinuation rates in those with ages 60 years and above versus below 60 years were 91% an d 68%, respectively. Conclusion In our cohort, the best-tolerated dose of regorafenib was 80 mg. Toxicity and intolerability of regorafenib lead to treatment discontinuation in nearly a quarter of patients. Patient age may influence tolerance and adherence to regorafenib. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.