Background
Immune checkpoint inhibitors are medications that activate anti-tumor responses by disrupting the inhibitory signaling to T cells. Nivolumab is an immune checkpoint inhibitor that ...selectively blocks the programmed cell death-1 (PD-1). Anti-PD-1 agents can breach immunologic tolerance. Fulminant diabetes is an immune endocrinopathy that results from a violent immune attack leading to complete destruction of pancreatic beta cells. We present a rare case of fulminant diabetes precipitated by anti-PD-1 immunotherapy.
Case
A 49-year-old male with a body mass index of 26.4 kg/m2, a history of Dandy–Walker syndrome and epilepsy, and no personal or family history of diabetes underwent left radical nephrectomy and retroperitoneal lymph node dissection for stage IV metastatic renal cell carcinoma (metastases to lungs). He received first-line sunitinib treatment for three months. He developed new hepatic metastasis, and a second-line treatment with nivolumab 3 mg/kg every two weeks was introduced. At 10 months of nivolumab, before the 22nd infusion, the patient suddenly complained of severe asthenia, somnolence, weight loss, polydipsia, and polyuria. Laboratory tests revealed potassium 4.2 mmol/L, sodium 138 mmol/L, bicarbonate 17.8 mmol/L, blood glucose 801 mg/dL, and arterial blood pH 7.27. He was diagnosed with diabetic ketoacidosis. Hemoglobin A1C was 10.9%. C-peptide was so low as 0.24. Glutamic acid decarboxylase autoantibodies, insulin autoantibodies and islet cell antibodies were all negative.
Conclusion
Anti-PD-1 immunotherapy is effective in the treatment of cancers. These agents can precipitate autoimmune disorders. As the use of anti-PD-1 agents is expected to rise, physicians should be educated about the potential side effects.
Background
Coronavirus disease 2019 (COVID-19) has quickly turned into a global pandemic with close to 5 million cases and more than 320,000 deaths. Cancer patients constitute a group that is ...expected to be at risk and poor prognosis in COVID pandemic. We aimed to investigate how cancer patients are affected by COVID-19 infection, its clinical course and the factors affecting mortality.
Methods
In our single-center retrospective study, we included cancer patients with laboratory confirmed COVID-19 in our hospital. Demographic, clinical, treatment, and laboratory data were obtained from electronic medical records. Logistic regression methods were used to investigate risk factors associated with in-hospital death.
Results
In the hospital, 4489 patients were hospitalized with COVID infection and 77 were cancer patients. The mean age of cancer patients was 61.9 ± 10.9 and 44 of them were male (62%). While the mortality rate in non-cancer patients was 1.51% (
n
= 68), this rate was significantly higher in cancer patients, 23.9% (
n
= 17). The stage of the disease, receiving chemotherapy in the last 30 days also lymphopenia, elevated troponin I,
d
-dimer, CRP, and CT findings were associated with severe disease and mortality. Severe lung involvement (OR = 22.9,
p
= 0.01) and lymphopenia (OR = 0.99,
p
= 0.04) are the most important factors influencing survival in logistic regression.
Conclusions
The disease is more severe in cancer patients and mortality is significantly higher than non-cancer patients. These data show that it may be beneficial to develop dynamic prevention, early diagnosis and treatment strategies for this vulnerable group of patients who are affected by the infection so much.
Candidemia is an important clinical condition that prolongs hospital stays and increases morbidity, mortality, and hospital costs. The aim of this retrospective study was to evaluate the ...epidemiological and microbiological characteristics of patients with candidemia between January 2013 and December 2019. Two hundred forty-one episodes of candidemia were observed in 230 patients, 45% of whom were female. The median age was 63 years, and 53.9% of the episodes were in the intensive care unit (ICU). Commonly observed predisposing factors for candidemia included antibiotic use (71.3%), urinary catheterization (56.3%), central venous catheter placement (50.3%), total parenteral nutrition (47.9%), solid-organ malignancy (46%), surgery (48.6%), chemotherapy (37%), and steroid treatment (25.5%). The crude mortality rate was 52.7%. A significant difference was found between survivors and non-survivors (P = 0.007) according to the Charlson Comorbidity Index. However, no statistically significant association was found between mortality and age, sex, surgical procedure, catheter-related candidemia, or Candida spp. infection. The most frequently isolated Candida sp. was C. albicans (51%). Overall resistance rates to fluconazole, voriconazole, caspofungin, micafungin, and flucytosine were 3.7%, 0%, 2.5%, 1.8%, and 1.8%, respectively. Consequently, there is a need for tests that provide higher success rates, rapid diagnosis of candidemia, and local epidemiological data on antifungal resistance.
Introduction
The foremost side effects of anti-PD-1 therapy are immune related and pancreatitis associated with nivolumab treatment has been rarely reported.
Case report
The patient was treating with ...subcutaneous insulin because of nivolumab induced diabetes mellitus. A patient was diagnosed metastatic renal cell carcinoma and treated with nivolumab. Diabetes mellitus and pancreatitis, which are immune-related adverse events were observed in the patient.
Management & outcome
After the diagnosis of nivolumab induced immune pancreatitis methylprednisolone 2 mg/kg per day intravenously started. After steroid treatment, the patient's complaints regressed, amylase and lipase levels began to decline.
Discussion
This case report highlights the possibility of different immune-related adverse events that can affect pancreas in all patients which were treated with ICIs.
Background
We report the case of a patient with melanoma and liver failure with encephalopathy, successfully treated with nivolumab without major side effects and encouraging prolonged disease ...control.
Case presentation
In June 2022, metastatic lesions appeared in the liver associated with melanoma progression under treatment. Liver biopsy was non-diagnostic. The patient developed fever, abdominal distension, and jaundice. Liver function tests (LFTs) began to deteriorate. Hepatic encephalopathy developed in accordance with the worsening liver functions in the patient. Upper abdominal MRI with primovist showed multiple, progressive, metastatic lesions in the liver and mild to moderate dilatation of the intrahepatic biliary tract. Patient was evaluated as acute cholangitis associated with the compression of the biliary tract by progressive liver metastases. In December 2022, the patient was started antibiotherapy for cholangitis and Nivolumab (240 mg flat dose, every 2 weeks) therapy. After the first dose, both LFT and constitutional symptoms began to improve. Subsequently, LFTs almost completely returned to normal, clinical response was achieved. Multiple metastatic lesions in the liver regressed in the radiological evaluation performed at the third month of nivolumab treatment. With partial response, nivolumab treatment is continued.
Conclusion
In this case is reported patient with hepatic encephalopathy due to an advanced refractory melanome successfully, and safely, treated with programed cell death-1 (PD-1) inhibitors. Clinical trials to explore the benefits of these immunotherapies in the hepatic failure population with advanced solid tumors should be supported.
Background
Nivolumab is an immune checkpoint inhibitor that selectively blocks the programmed cell death-1. Nowadays, immune checkpoint inhibitors such as nivolumab are used in the treatment of many ...different types of cancer. Treatment responses of these agents may be different from standard chemotherapy, and hyperprogression is a new entity that occurs with immune checkpoint inhibitors. We present a case of hyperprogressive disease precipitated by anti-programmed cell death-1 immunotherapy.
Case Report
A 25-year-old woman was treated with ipilimumab, dabrafenib plus trametinib, and nivolumab, respectively, for stage IV melanoma. Palliative whole brain radiotherapy was completed due to brain metastases before the administration of nivolumab. After the fourth cycle of nivolumab, the patient’s general condition deteriorated and control positron emission tomography/computed tomography confirmed hyperprogression. Also, brain magnetic resonance imaging indicated the hyperprogression of the metastatic lesions.
Management and Outcome
After brain magnetic resonance imaging and positron emission tomography/computed tomography showed the hyperprogressive disease, nivolumab was discontinued. Cisplatin and dacarbazine were initiated for melanoma.
Discussion
Anti-programmed cell death-1 immunotherapy is effective in cancers. These agents can precipitate hyperprogressive disease. As the use of anti-programmed cell death-1 agents is expected to rise, physicians should be educated about the potential possibility of hyperprogression during the immunotherapy.
Objective
Familial Mediterranean fever (FMF) is an auto-inflammatory disease that is also characterized with some of the common musculoskeletal features of spondyloarthritis (SpA). Enthesitis is the ...hallmark of SpA. Recently, it was postulated that exertional leg pain is a possible sign of lower extremity enthesitis associated with FMF severity. In this study, we have evaluated the association between the enthesitis, enthesitis score and disease severity in FMF patients.
Methods
We enrolled 238 FMF patients that fulfilled the modified Tel-Hashomer criteria. We assessed the presence of enthesitis at the Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) defined sites with standard palpation method. Then, FMF patients dichotomised two groups as enthesitis group and controls. Herein, we evaluated the enthesis extensity with MASES. FMF disease severity was determined via the international severity scoring system for FMF (ISSF). Firstly, we have compared demographic properties, disease-related features and ISSF scores of the groups. Then, we have correlated ISSF with MASES in enthesitis group.
Results
We showed that 54 (22.6%) of 238 patients had enthesitis. The demographic features were similar between the groups. The enthesitis group had higher ISSF scores (
p
< 0.001); higher frequency of fever (
p
= 0.004), exertional leg pain (
p
< 0.001), myalgia (
p
< 0.001) and arthritis (
p
= 0.01); and more intense, widespread, frequent and longer attacks compared with controls. Moreover, there was a weak correlation between ISSF and MASES in the patients with enthesitis.
Conclusion
Enthesitis may be a sign of more severe FMF phenotype and frequently associated with other musculoskeletal manifestations resemble SpA.
Key points
•More than one-fifth of the patients with FMF would suffer from enthesitis.
•The FMF patients with enthesitis had higher ISSF scores; higher frequency of fever, exertional leg pain, myalgia and arthritis; and more intense, widespread, frequent and longer attacks as compared with controls.
•Enthesitis may be a sign of more severe FMF phenotype and frequently associated with other SpA-like musculoskeletal feature.
Introduction
Patients with distant metastatic melanoma has a poor prognosis, with a reported median survival time of six to eight months. In modern era, survival has prolonged with the immunotherapy ...and targeted therapy options. Potent and selective BRAF inhibitors have been developed that specifically inhibit mutated BRAF over other RAF kinases. Vemurafenib was the first selective tyrosine kinase inhibitor developed to target the V600E allele of BRAF-mutant melanoma.
Case Report
In this report, we present a case of BRAFV600E-mutant metastatic melanoma, which is being treated with vemurafenib monotherapy with complete response for about seven years.
Management and Outcome
The patient is still being treated with vemurafenib and radiologic complete response is ongoing for about seven years.
Discussion
Patients treated with BRAF inhibitors monotherapy had promising response rates and improvement in the progression-free survival and overall survival, but melanoma cells became resistant very quickly, affecting the progression. In this case, we present a case that has permanent response to vemurafenib monotherapy.
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•Vertically aligned CNTs successfully grown on aluminum substrates.•Catalyst assisted CVD process developed in a hot-filament chamber.•Conventional microfabrication process used to ...create an array layout.•3D micropatterned CNT array provides >10× area for incorporating cathode material.
Attempts to grow carbon nanotubes directly on to aluminum (Al) substrates have had limited success, primarily due to its relatively low melting point of 660°C. In this work, we have successfully synthesized vertically aligned CNTs (VACNTs) in a planar configuration (48µm tall) as well as, for the first time, a micropatterned array with 36µm tall CNTs on Al substrates. This was achieved by combining conventional microfabrication steps for patterning an array and a catalyst-assisted hot-filament CVD process with methane as carbon source gas for CNT synthesis. Such substrates can provide highly conductive and high specific surface area host materials for cathodes in lithium ion batteries and supercapacitors. We have demonstrated a >10× increase in surface area available for coating cathode nanoparticles in the 3D micropatterned CNT array, as compared to the planar configuration.
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