Immune checkpoint inhibitors have ushered in a new era in cancer management. Nivolumab is a human immunoglobulin G4 (IgG4) monoclonal antibody that selectively inhibits programmed cell death-1 (PD-1) ...activity by binding to the PD-1 receptor. This inhibits suppression of the T-cell activity, which can in turn cause increased killing of cancer cells. This alteration in the activity of the T cells can cause them to lose their ability to identify host cells and leads to immune-related adverse effects (irAE). Nivolumab-induced hepatotoxicity is rare and accounts for 3–6% of all irAE. We present a case of nivolumab-induced hepatitis. A woman who was treated for recurrent renal cell carcinoma presented with hepatitis. Workup for other causes was negative and the hepatitis was attributed to the administration of nivolumab. She was started on oral steroids followed which she initially improved. However, she later presented with massive upper gastrointestinal bleeding secondary to gastroduodenal ulcers and subsequently developed acute tubular necrosis and passed from the complications. Immune checkpoint inhibitors have proven to be a promising approach in the management of a wide array of neoplasms by immunomodulation. As these agents are becoming standard of therapy in the management of cancers, a heightened vigilance in the diagnosis of irAE is warranted. With heightened vigilance, early recognition can lead to decreased mortality and morbidity.
The aim of this paper is to review and discuss the background, common manifestations, differential diagnosis, and current treatment practices of reactive arthritis. The focus will be on the choice of ...therapy in patients with poor prognostic factors. A PubMed search was performed in March 2020 on reactive arthritis and revealed 137 articles. Fourteen case reports and four large-scale studies that are pertinent for discussion in terms of treatment of reactive arthritis over the past five years are reported along with poor prognostic markers. The first choice of therapy regardless of the number of poor prognostic markers is non-steroidal anti-inflammatory drugs (NSAIDs). The second choice of therapy appeared to be glucocorticoids in the oral as well as intra-articular forms. No correlation was detected between the need for systemic steroids and the number of poor prognostic factors present. The third choice of therapy appears to be disease-modifying anti-rheumatic drugs (DMARDs) (such as sulfasalazine) and their increasing use can be demonstrated over time. Novel therapies such as adalimumab have also been shown to be used and this shows a strong correlation with an increased number of poor prognostic factors. Reporting of these case reports and review of literature contribute to knowing more about reactive arthritis and help keep us up to date with newer therapies available when patients do not respond to conventional therapy. It was notable that the increased number of poor prognostic factors and non-responders have shown increased use of tumor necrosis factor inhibitors (TNFI) such as adalimumab.
Background
Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease (CVD) as well as with an increased risk of chronic kidney disease (CKD), also a known ...cardiovascular risk factor. However, it is not known if RA is a predictor of adverse outcomes in patients with CKD. We hypothesized that among a cohort of patients with CKD, RA would be associated with an increased risk of mortality.
Materials and methods
We conducted a retrospective study of 3939 participants with CKD from the prospective Chronic Renal Insufficiency Cohort (CRIC) study. The primary outcome of interest was all-cause mortality. Secondary outcomes included CKD progression (defined as end-stage kidney disease or 50% decline in estimated glomerular filtration rate), cardiovascular endpoints, and composite of myocardial infarction, cerebrovascular accident, heart failure, or death. Multivariable Cox proportional hazards regression was utilized, adjusting for potential confounders including age, sex, race/ethnicity, body mass index, current smoker, and education.
Results
The study cohort included 83 participants with RA on a disease modifying anti-rheumatic drug (DMARD). In the adjusted analysis, CKD-RA status was significantly associated with an increased risk of death (adjusted HR, aHR, 1.73 (1.27, 2.35)) and composite outcome (aHR 1.65 (1.27–2.15)) even after adjusting for traditional risk factors. Similar statistically significant associations were observed between CKD-RA and other secondary outcomes except for CKD progression.
Conclusion
RA was associated with higher mortality among individuals with CKD but not progressive renal decline. Further studies evaluating the mechanisms behind this association are needed.
Key Points
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Rheumatoid arthritis (RA) is associated with an increased risk of cardiovascular disease (CVD) as well as with an increased risk of chronic kidney disease (CKD), also a known cardiovascular risk factor. However, it is not known if RA is an independent predictor of adverse outcomes in patients with CKD
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In this study, we observed that CKD patients with RA experience higher mortality as well as an increased risk of CVD compared to patients with CKD without comorbid RA
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These data provide rationale for more aggressive monitoring for CVD in patients with CKD and RA. They also underscore the need for determining which interventions can help decrease the burden of mortality in these patients
•Non-publication of clinical trials leads to publication bias.•First study that looks at the publication rate of cancer clinical trials in CTRI.•Close to half of cancer clinical trials registered in ...CTRI remain unpublished.•Trials funded by international pharmaceuticals are more likely to be published.•Trials conducted at a multinational level are more likely to be published.
Non-publication of clinical trials gives rise to publication bias which distorts data available in medical literature. Prior research indicates that a large number of clinical trials remain unpublished. We conducted a study to determine the publication rate of clinical trials related to cancer which were registered in the Clinical Trials Registry-India (CTRI), the clinical trials registry of India.
We performed a cross-sectional analysis of CTRI to determine publication rates. We searched CTRI for completed interventional clinical trials related to cancer. A comprehensive search for publications of the registered trials was performed by three different investigators. We considered a trial to be published if the study or any outcome data pertaining to the study was accepted for publication in a peer-reviewed journal.
73 of the 133 trials (54.9 %) included in our study were published. Randomized controlled trials were more likely to be published than non-randomized trials (61 % vs 34 %, p 0.007). Trials funded by international pharmaceutical companies were more likely to be published than the ones by Indian pharmaceutical companies (72 % vs 24 %, p < 0.00001). Trials conducted at a multinational level were more likely to be published than the ones conducted only in India (84 vs 37 %, p < 0.00001).
Large number of cancer clinical trials remain unpublished. This could be due to reluctance on the part of the investigator to publish statistically non-significant results, and sometimes to protect intellectual property. There is much scope for improvement in the rates of trial publication and information dissemination.
Idiopathic granulomatous mastitis (IGM) is a chronic inflammatory disease of the breast, the etiology of which, has still not been elucidated. There have been several mechanisms proposed to explain ...the pathogenesis. Since the first description of the disease, it has proved itself to be a great diagnostic and therapeutic challenge. It is very often misdiagnosed as cancer, resulting in myriad workup by the physician and great distress to the patient. Clear guidelines as to the management have still not been described. Here, we describe two patients who presented with IGM and have been successfully treated. The first patient was treated with a combination of steroids and antibiotics. The second patient achieved remission of the disease with antibiotics alone. We also propose an algorithm for the management of IGM.
Statins are a group of frequently-prescribed drugs with proven cardiovascular risk-benefit. The most common adverse effects include weakness and myalgias. However, prescribers need to be aware of a ...less common complication, statin-associated necrotizing myopathy, which can occur at any time during the treatment course and has been found to be <0.1% of adverse effects. High suspicion is warranted when patients taking statins develop weakness and myalgia. Increased risk of muscle injury has been observed when using gemfibrozil in combination with statins and should be avoided. We present a case of an elderly male with chronic use of combination lipid-lowering agents who initially presented with proximal weakness. He was diagnosed with statin-associated necrotizing myopathy and subsequently developed rapid end-stage renal disease in the setting of severe rhabdomyolysis. The case report discusses the work-up of proximal muscle weakness with focus on the importance of early recognition and prompt management of rhabdomyolysis to avoid life-threatening complications.
Cervical cancer is the fourth most common cancer in females. Clear cell adenocarcinoma of the cervix is an uncommon histological variant and is usually seen with intrauterine exposure to ...diethylstilbestrol. A 28-year-old female with no intrauterine exposure to diethylstilbestrol presented with postcoital bleeding. A pelvic exam revealed a cervical mass. Imaging confirmed the cervical mass and positron emission tomography scan showed an increased uptake in the cervical mass as well as the para-aortic and pelvic lymph nodes. Biopsy showed a clear cell carcinoma of the cervix. She was treated with cisplatin and paclitaxel for eight cycles and concurrent radiation therapy. She had a complete response to therapy and has been in complete remission nine months from the end of therapy. There are no clear guidelines for the treatment of clear cell carcinoma with current therapy based on the treatment of squamous and non-clear cell adenocarcinoma. Cisplatin and paclitaxel could be an option, given the successful treatment of the patient in our case.
Levamisole is a common contaminant in cocaine and has led to the emergence of an entity known as levamisole-induced vasculitis (LIV). There is no consensus on the management of this condition. We ...describe a patient who presented with acute on chronic LIV who was treated with pulse dose steroids. We aim to discuss the diagnosis and current management options for LIV. We have compared seven case reports that have measured C-reactive protein (CRP) and compared the CRP levels, site involved, dose, and mode of steroid administration. We postulate that elevated CRP may warrant steroid therapy over conservative management and could lead to a possible decreased hospital stay.
Leukocytoclastic vasculitis (LCV) is an uncommon condition with a broad differential diagnosis. Although the clinical history, physical examination, and laboratory workup are pivotal when formulating ...a differential diagnosis of LCV, a skin biopsy is required in most cases to elucidate the cause. The diagnostic yield of a skin biopsy increases within the first 24 to 48 hours of the lesion onset indicating the importance of obtaining a prompt skin sample. We present the case of a 60-year-old man who presented to the emergency department with a three-day history of fevers, headaches, and a painful skin rash. He endorsed rhinorrhea and sore throat a week ago. Physical examination was notable for an erythematous papular rash with palpable violaceous purpura located mainly at the distal right leg and thigh. He also complained of painful bilateral hand edema. His complete blood count and chemistries were unremarkable. His C-reactive protein was 147 mg/L (normal value <8 mg/L), and sedimentation rate was 51 mm (normal value <15 mm). Immunoglobulin A was 509 mg/dL (normal value 82-460 mg/dL). Further workup including viral hepatitis serologies, antinuclear antibodies, complements, antineutrophil cytoplasmic antibodies, cryoglobulins, rheumatoid factor, and blood cultures yielded negative results. Therefore, it was believed that his rash was likely associated with his recent upper respiratory infection. A skin biopsy done on the first day of admission was positive for LCV without immunoglobulin A deposition. He was managed with prednisone and anti-inflammatory medications with improvement of his rash.
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