Immune Checkpoint Inhibitor-Associated Myocarditis: A Literature Review.

Recently in the field of oncology, immune checkpoint inhibitors (ICI) are being increasingly utilized both in clinical trials and in clinical practice. It is a form of biological therapy that targets tumors by activating the immune system, which in turn eliminates proliferating cancer cells. These have numerous immune-related adverse events (irAEs), one of which is myocarditis, which has high rates of mortality. This article was a narrative review of myocarditis related to ICI use.  Studies from the PubMed, Cochrane, and American Society of Clinical Oncology (ASCO) databases were used in writing this review. The databases were searched for original publications for adverse effects related to ICI use and myocarditis specifically. There are numerous published instances of cancer immunotherapy causing myocarditis. ICI therapy has numerous benefits, as it upregulates the immune system to target cancer cells, utilizing the body's own defense mechanisms to target proliferating cells. Myocarditis is a serious side effect, however. Therefore, on balance, these monotherapies are worth using. While this literature review primarily identifies cross-reaction as the main mechanism of myocarditis, there are other possible mechanisms. One proposed mechanism involves a shared antigen between the myocardial tissue and the tumor. This mechanism is called molecular mimicry, where the monoclonal antibody attacks both the myocardial tissue and the tumor cell. Management of ICI-induced myocarditis has not been studied by randomized controlled trials or prospective studies, but based on previous case reports and case series it is mostly treated with steroids initially. An ICI rechallenge after temporary discontinuation appears conceivable in many cases, especially given its therapeutic effects, but only limited data are available on the safety of a rechallenge after an irAE. The lack of RCTs regarding rechallenge with an ICI after irAE, more so specifically about myocarditis, along with the overall results and the complexity involved in such cases once again emphasize the need to make decisions on an individual basis by a multidisciplinary expert working group. At the same time, the focus should also be on publishing more data as the need will grow along with the indications for ICI therapies.

Efficacy of tafamidis in transthyretin amyloid cardiomyopathy: a systematic review and meta-analysis.

In May 2019, the U.S. Food and Drug Administration approved tafamidis as the first conservative management of transthyretin amyloid cardiomyopathy (ATTR-CM). Our aim in conducting this systematic review and meta-analysis was to assess the efficacy of tafamidis on patients with ATTR-CM. For that purpose, we thoroughly searched PubMed, ScienceDirect, and Clinical trails.gov by using the appropriate search strategy and following predefined inclusion and exclusion criteria, which retrieved 235 articles initially. Of which two randomized controlled trials (RCTs) and one observational study matched our inclusion criteria. A total of 876 patients are included in this analysis. Based on results, tafamidis significantly reduced cardiovascular (CV) mortality in the ATTR-ACT trial and Ochi et al. (OR 0.58; 95% CI: [0.41-0.83], P=0.003, I 2=87%). A subgroup analysis was conducted for CV mortality due to heart failure (OR 0.89; 95% CI: [0.63-1.25], P=0.50, I 2=93%). The results exhibit that tafamidis reduced all causes of mortality (OR 0.45; 95% CI: [0.32-0.64], P≤0.00001, I 2=22%). Furthermore, mortality remained statistically insignificant in patients with heart transplants (OR 1.18; 95% CI: [0.52-2.70], P=0.70, I 2=0%) and patients with cardiac mechanical assist devices (OR 4.15; 95% CI: [0.48-35.66], P=0.20, I 2=0%). This meta-analysis suggests that tafamidis is a safe and efficient drug to use in patients with ATTR-CM and can possess the potential to be a milestone in enhancing the conservative management of the patients.

'Immune-inflammatory markers & clinical characteristics for outcomes in hospitalized SARS-CoV-2 infected patients of Pakistan: a retrospective analysis'.

OBJECTIVE: Accumulating evidence suggests the role of immune-inflammatory markers in early risk stratification and prognostication of COVID-19 patients. We aimed to evaluate their association with severity and the development of diagnostic scores with optimal thresholds in critical patients. SETTING AND PARTICIPANTS: This retrospective case study includes hospitalized COVID-19 patients from March 2019 to March, 2022, in the developing area teaching hospital in Pakistan. Polymerase chain reaction (PCR) positive patients, n = 467 were investigated for clinical outcomes, comorbidities and disease prognosis. The plasma levels of Interleukin-6 (IL-6), Lactate dehydrogenase (LDH), C-reactive protein (CRP), Procalcitonin (PCT), ferritin and Complete blood count markers were measured. RESULTS: Majority were males (58.8%) and patients with comorbidities had more severe disease. Hypertension and diabetes mellitus were the commonest comorbidities. Shortness of breath, myalgia and cough were the main symptoms. The hematological markers NLR, as well as the plasma levels of immune-inflammatory variables, IL-6, LDH, Procalcitonin, Erythrocyte sedimentation rate, Ferritin were markedly raised in severe and critical patients (p < 0.0001 for these markers). ROC analysis supports IL-6 as the most accurate marker with high prognostic relevance with proposed cut-off threshold (43 pg/ml), determining >90% of patients in terms of COVID-19 severity (AUC = 0.93, 91.7%, se; 90.3%sp). Furthermore, positive correlation with all other markers including NLR with cut-off = 2.99 (AUC = 0.87, se = 89.8%, sp = 88.4%), CRP with cut-offs at 42.9 mg/l, (AUC = 0.883, se = 89.3% and sp = 78.6%), LDH cut-off at 267µg/L, evidenced in >80% patients (AUC = 0.834 se = 84% and sp = 80%). Additionally, ESR and ferritin have the corresponding AUC 0.81 and 0.813 with cut-off at 55 mm/hr and 370, respectively. CONCLUSION: Investigating the immune-inflammatory markers can assist physicians in providing prompt treatment and ICU admission in terms of COVID-19 severity. As a result, which may reduce the overall mortality of COVID-19 patients.

Treatment with Testosterone Therapy in Type 2 Diabetic Hypogonadal Adult Males: A Systematic Review and Meta-Analysis.

Testosterone replacement therapy (TRT) has been used to treat hypogonadal males with type 2 diabetes mellitus (T2DM) for a long time, despite variable results. This meta-analysis examines TRT's role in hypogonadal males with T2DM. The databases PubMed, Embase, and Google Scholar were searched for relevant RCTs and observational studies. Estimated pooled mean differences (MDs) and relative risks with 95% confidence intervals were used to measure the effects of TRT (CIs). When compared to the placebo, TRT improves glycemic management by significantly reducing glycated hemoglobin (HBA1c) levels (WMD = -0.29 [-0.57, -0.02] p = 0.04; I2 = 89.8%). Additionally, it reduces the homeostatic model assessment levels of insulin resistance (WMD = -1.47 [-3.14, 0.19]; p = 0.08; I2 = 56.3%), fasting glucose (WMD = -0.30 [-0.75, 0.15]; p = 0.19; I2 = 84.4%), and fasting insulin (WMD = -2.95 [-8.64, 2.74]; however, these results are non-significant. On the other hand, HBA1c levels are significantly reduced with TRT; in addition, total testosterone levels significantly increase with testosterone replacement therapy (WMD = 4.51 [2.40, 6.61] p = 0.0001; I2 = 96.3%). Based on our results, we hypothesize that TRT can improve glycemic control and hormone levels, as well as lower total cholesterol, triglyceride, and LDL cholesterol levels while raising HDL cholesterol in hypogonadal type 2 diabetes patients. To this end, we recommend TRT for these patients in addition to standard diabetes care.

Efficacy, safety and cost-effectiveness of vonoprazan vs Proton Pump Inhibitors in reflux disorders and H. pylori eradication: A literature review.

Gastroesophageal reflux disease (GERD) is one of the most prevalent conditions worldwide and is conventionally treated by proton pump inhibitor therapy. However, around 40% of people have reported some form of resistance to this therapy. Vonoprazan has recently been approved for the treatment of GERD. Literature was searched on PubMed, Google Scholar, Embase and Medline. Inclusion criteria were 1) Human subjects; 2) papers published in English language; 3) study types that are RCTs. In pre-clinical studies, VPZ was unaffected by changes in pH, making it 1.2-2 times more potent than PPI, both in-vivo and in-vitro. In studies involving GERD, several RCTs proved higher efficacy of VPZ than conventional PPI. RCTs on patients affected by H. Pylori showed a higher efficacy than VPZ (95.8%) as compared to PPI (69.6%). In another RCT, adverse effects including diarrhea, nausea and body rash were observed in 32.7% of the people taking VPZ as compared to 40.5% of the people taking PPI. VPZ was shown to be much more cost effective as compared to PPI. This article concludes that VPZ is superior to PPI in terms of efficacy, safety and cost-effectiveness in reflux disorders and H. pylori eradication. Hence, use of vonoprazan should be preferred over conventional PPIs in these disorders. As most of the research was conducted in Japan, studies should be carried out in different regions of the world to explore if these results are extrapolated in those regions. Research is also needed to explore the efficiency of VPZ in scenarios of PPI resistance.

Chronic Suppurative Otitis Media leading to cerebellar brain abscess, still a problem in 21st century: A case report.

Introduction and importance: Chronic suppurative otitis media (CSOM) is a chronic inflammation of the middle ear associated with tympanic membrane rupture and purulent discharge for at least 6 weeks. Owing to the proper use and easy availability of antibiotics, these types of cases are rare in developed regions, but they are still occasionally seen in the developing world with poor hygiene and a lack of availability of antibiotics and immunizations. Case presentation: Patient presented with complaints of headache, yellow-colored discharge from ear, fever and vomiting. The patient's Glasgow Coma Scale (GCS) was 12/15, neck stiffness and positive Kernig's sign, horizontal nystagmus and exaggerated deep tendon reflexes. Positive CSF findings and Magnetic Resonance Imaging showing right sided cerebellar abscesses, led to the diagnosis of right-sided CSOM leading to cerebellar brain abscess. Patient was treated with anti-pyrectics, intravenous mannitol, IV and topical antibiotics and IV-dexamethasone. Abscess evacuation was performed in neurosurgery department while mastoidectomy was performed in ENT department. Patient's condition improved quickly and was discharged with regular follow-up. Discussion: CSOM is a long-standing middle ear infection, associated with ear discharge and permanent perforation of the tympanic membrane. Divided into two main types, a) Tubo tympanic b) Atticoantral. CSOM occasionally presents with severe intracranial complications, especially in developing countries. Conclusion: CSOM is a chronic inflammation of the middle ear. Without early and effective management, it can lead to serious intracranial complications. So, diagnosis of complications like cerebellar abscess should be on the differential while dealing with patients with CSOM in developing countries.

Parvovirus b19-Induced Acute Hepatitis With Hepatosplenomegaly and Polyarthropathy.

Parvovirus B19 infection can present with myriads of clinical diseases and syndromes; hepatitis and polyarthropathy are a few of these examples. Parvovirus frequently affects children but this condition has also been reported in adults.  The present case report discusses a case of a 43-year-old female who presented to the outpatient department (OPD) with complaints of high-grade fever and pain in multiple joints of her body for three days. On examination, stiffness and swelling of the hand, knees, wrist, and ankles were noted. Laboratory investigations showed highly elevated aspartate transaminase (AST), alanine transaminase (ALT), and bilirubin. Electrocardiogram (ECG) and echocardiogram (ECHO) findings were unremarkable. PCR testing showed the presence of parvovirus. Parvovirus B19 infection led to the development of acute hepatitis, which appeared as yellowing of skin (jaundice) and led to hepatosplenomegaly. Parvovirus-induced polyarthropathy was also observed in the patient. The patient was managed with a parenteral course of ceftriaxone, paracetamol, and a normal saline infusion. Anti-viral drugs were also prescribed to the patient including ribavirin and pegylated interferon. This case study will explore how the patient was diagnosed and managed with conventional therapy and anti-viral to relieve parvovirus-induced hepatitis with hepatosplenomegaly and polyarthritis. Acute hepatitis can be caused by viruses and other noninfectious causes, all of which must be cleared out to avoid chronic disease development. When patients present with joint pain and skin rashes, a thorough workup for viral indicators, medication histories, autoimmune and metabolic illnesses, and parvovirus b19 infection is required.

Statin-Induced Thrombocytopenia in a Young Female: A Case Report and Literature Review.

The causal relationship of thrombocytopenia with statin intake has been described in many research articles. Our case discusses the refractory nature of thrombocytopenia in a 22-year-old female, one month following a daily intake of 20 mg atorvastatin. This is the first case ever of drug-induced refractory thrombocytopenia reported in a young patient. We will also discuss previously reported cases of drug-induced thrombocytopenia (DIT) in our manuscript.