Safety and Efficacy of Trastuzumab Deruxtecan for Metastatic HER2+ and HER2-low Breast Cancer: An Updated Systematic Review and Meta-Analysis of Clinical Trials.

OBJECTIVES: Trastuzumab deruxtecan (T-DXd) is a novel antibody-drug conjugate (ADC) promising in treating metastatic HER2+ and HER2-low breast cancer. This updated systematic review and meta-analysis, integrating data from the latest clinical trials, aimed to evaluate the safety and efficacy of T-DXd in this patient population. METHODS: We adhered to the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. A comprehensive search was conducted across PubMed, Scopus, and Web of Science up to January 2024, focusing on clinical trials that assessed T-DXd's efficacy and safety. Eligibility criteria were based on the PICOS framework, and selected studies underwent rigorous quality assessment and data extraction. The primary outcomes were progression-free survival (PFS), overall survival (OS), and the incidence of adverse events. A random-effects meta-analysis was performed to synthesize the data. RESULTS: Seven studies involving 2,201 patients met the inclusion criteria. The pooled analysis revealed that T-DXd significantly improved PFS (OR=0.37, 95% CI: 0.27-0.52), indicating a robust efficacy in slowing disease progression. However, treatment was associated with an increased risk of anemia (OR=2.10, 95% CI: 1.36-3.25), fatigue (OR=1.56, 95% CI: 1.21-2.02), nausea (OR=6.42, 95% CI: 4.37-9.42), vomiting (OR=6.21, 95% CI: 3.14-12.25), constipation (OR=2.26, 95% CI: 1.53-3.34), and notably, drug-related interstitial lung disease (OR=10.89, 95% CI: 3.81-31.12). The efficacy outcomes demonstrated significant heterogeneity, which was addressed through sensitivity analysis. CONCLUSIONS: T-DXd shows significant efficacy in treating metastatic HER2+ and HER2-low breast cancer, offering a valuable therapeutic option for patients with advanced disease. However, the treatment is associated with notable adverse events, including a heightened risk of ILD. These findings underscore the need for careful patient selection, monitoring, and management strategies to mitigate risks. Future research should focus on optimizing treatment protocols and exploring methods to enhance safety profiles.

Efficacy of Sacituzumab Govitecan in Hormone Receptor-Positive/Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: A Comprehensive Systematic Review and Meta-analysis.

OBJECTIVES: Breast cancer is the most diagnosed cancer in women, with hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) being the predominant subtype. Sacituzumab govitecan (SG), a novel antibody-drug conjugate, has emerged as a promising treatment for metastatic HR+/HER2- breast cancer. This systematic review and meta-analysis aimed to evaluate its efficacy and safety. METHODS: Adhering to "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" guidelines, a comprehensive search was conducted in PubMed, Scopus, and Cochrane databases up to December 2023. We included clinical trials and observational studies evaluating SG in patients with HR+/HER2- advanced breast cancer. The primary outcome was progression-free survival (PFS). In contrast, the secondary outcomes included overall survival, objective response rate, clinical benefit rate, duration of response (DOR), and adverse event profiles. Review Manager (Version 5.4) was used for the statistical analysis. RESULTS: Nine studies met the inclusion criteria for systematic review; 2 were suitable for meta-analysis. The pooled analysis showed a hazard ratio of 0.53 (95% CI: 0.34-0.83; P= 0.005; I2 = 86%) for PFSl and a hazard ratio of 0.63 (95% CI: 0.36-1.11; P= 0.11; I2 = 92%) for overall survival. The pooled analysis of the duration of response showed significant results with a standard mean difference = 0.22 (95% CI: 0.03-0.42; P = 0.02; I2 = 61%). CONCLUSION: SG demonstrates significant benefit in PFS and duration of response in patients of HR+/HER2- advanced breast cancer.

Optimization Strategies in CAR T-cell Therapy: A Comprehensive Evaluation of Cytopenia, HLH/MAS, and Other Adverse Events.

Chimeric antigen receptor (CAR) T-cell therapy has emerged as a transformative treatment for various hematological malignancies. Still, its remarkable efficacy is accompanied by unique adverse events that must be carefully managed. This comprehensive literature review evaluates the safety profile of CAR T-cell therapy, focusing on cytopenia, hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS), and other potential complications. Cytopenia, characterized by reduced blood cell counts, affects a significant proportion of patients, with rates of anemia, neutropenia, and thrombocytopenia reaching up to 60%, 70%, and 80%, respectively. Risk factors include high tumor burden, prior chemotherapy, and bone marrow involvement. Cytokine release syndrome (CRS) occurs in 13% to 77% of patients and is linked to the cytokine storm induced by CAR T cells, target antigen expression, and preexisting immune dysregulation. Other notable adverse events discussed are cytokine release syndrome, neurotoxicity, and infections. Understanding the mechanisms, risk factors, and management strategies for these adverse events is crucial for optimizing patient outcomes and unlocking the full potential of this revolutionary therapy. The review highlights the need for continued research, interdisciplinary collaboration, and evidence-based approaches to enhance the safety and efficacy of CAR T-cell therapy.

The Efficacy of Tafolecimab in Chinese Patients with Hypercholesterolemia: A Systematic Review and Meta-analysis.

BACKGROUND: Cardiovascular disease was the leading cause of death worldwide in 2021, with atherosclerotic cardiovascular disease, encompassing hypercholesterolemia, being a major contributing factor. A range of lipid-lowering medications is used for the management of hyperlipidemia, but the use of statins is considered as standard therapy. Unfortunately, some patients do not respond to this therapy, necessitating novel therapeutic approaches. Tafolecimab is a novel proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody that inhibits the binding of PCSK9 with low-density lipoprotein receptors (LDLRs) and increases LDLR recycling, and thus it indirectly lowers circulating low-density lipoprotein cholesterol (LDL-C) levels by increasing LDL-C uptake. The primary objective of this study is to assess the efficacy of tafolecimab in reducing LDL-C levels. METHODS: A thorough search was conducted on Medline (PubMed), Cochrane CENTRAL, Scopus, and Google Scholar from inception until December 2023. Review Manager was used for statistical analysis. The random effects model was used to calculate risk ratios (RRs), mean differences (MDs), and 95% confidence intervals (CIs). Heterogeneity was assessed using the Higgins I2 index. The risk of bias was assessed using Cochrane's RoB 2 tool. This review has been registered with PROSPERO (CRD42023471020). RESULTS: A total of four Chinese studies matched the inclusion criteria and were included in this review. A total of 726 patients were included in this review, out of which 476 patients were males. Out of four, three studies that studied the efficacy of 450 mg tafolecimab every 4 weeks in patients (n = 462) as compared to placebo (n = 224) were included in the meta-analysis. According to the pooled results, tafolecimab caused a significant decrease in LDL-C levels from baseline to week 12 as compared to placebo (MD = - 63.78, 95% CI - 65.88 to - 61.68, p value < 0.00001, I2 = 97%). The pooled results showed that more patients achieved ≥ 50% reductions in LDL-C levels (RR = 52.33, 95% CI 18.51-147.95, p value < 0.00001, I2 = 0%) and LDL-C < 1.8 mmol/L (RR = 17.27, 95% CI 9.59-31.11, p value < 0.00001, I2 = 0%) at week 12 in the tafolecimab group than the placebo group. Additionally, tafolecimab also caused a robust decrease in non-HDL-C, apolipoprotein B, and lipoprotein(a) levels from baseline to week 12 compared to placebo. The overall risk of bias was low, as determined by the RoB 2 tool. CONCLUSIONS: Tafolecimab showed promising lipid-lowering efficacy and a well-tolerated safety profile. Our findings suggest its potential as an innovative therapeutic option for individuals with hypercholesterolemia; however, significant heterogeneity was observed in some results, making it difficult to come to a firm conclusion. Therefore, large-scale randomized trials are required to confirm our findings, particularly exploring the most effective dosage regimens across varied populations. REGISTRATION: PROSPERO identifier number CRD42023471020.

Efficacy and Safety of BRCA-targeted Therapy (Polyadenosine Diphosphate-ribose Polymerase Inhibitors) in Treatment of BRCA-mutated Breast Cancer: A Systematic Review and Meta-analysis.

Breast cancer is the second leading cause of women's cancer deaths after lung cancer. Risk factors such as environment, lifestyle, and genetics contribute to its development, including mutation in the breast cancer (BRCA) gene. Polyadenosine diphosphate-ribose polymerase inhibitors (PARPi) target these mutations, benefiting patients with advanced cancers. This review summarizes PARPi' safety and efficacy in the treatment of BRCA-mutated breast cancer. PubMed, The Cochrane Library for Clinical Trials, and Science Direct, were searched for articles from inception to April 2024. Eligible articles were analyzed, and data were extracted for meta-analysis using RevMan 5.4 software with a random-effect model. Out of 430 articles identified from online databases, only 6 randomized control trials including 3610 patients were included in the analysis. PARPi therapy improved progression-free survival (hazard ratio: 0.64; 95% CI: 0.56, 0.73; P< 0.00001) and overall survival (hazard ratio: 0.84; 95% CI: 0.73, 0.98 P = 0.02), according to the analysis. In our safety analysis, the risk of adverse events was not statistically different between PARPi versus chemotherapy (relative risk [RR]: 1.08; 95% CI: 0.44, 2.68; P = 0.86), and combined PARPi and standard chemotherapy (RR: 1.00; 95% CI: 0.93, 1.07; P = 0.80). The only statistically significant difference was observed in anemia, where PARPi increased the risk of developing anemia compared with standard chemotherapy (RR: 6.17; 95% CI: 2.44, 15.58; P = 0.0001). In BRCA-mutated breast cancer, PARPi treatment shows better overall survival and progression-free survival compared with standard chemotherapy or placebo. Furthermore, PARPi, either alone or in combination therapy, does not increase the risk of adverse events in these patients, as per the meta-analysis.

Rituximab as a Therapeutic Strategy in Hemophagocytic Lymphohistiocytosis: Efficacy, Outcomes, and Survival-Insights From a Systematic Review.

BACKGROUND: Hemophagocytic lymphohistiocytosis (HLH) is a severe immunologic disorder that can be fatal if left untreated. The condition is characterized by excessive immune system activation and is often triggered by infections such as Epstein-Barr virus (EBV). Rituximab, an anti-CD20 monoclonal antibody, has been suggested as a treatment, particularly for EBV-associated HLH. METHODS: A systematic review was conducted using PRISMA guidelines, with a literature search spanning PubMed, Scopus, Web of Science, and the Cochrane Library. The inclusion criteria focused on studies that assessed rituximab's efficacy in treating HLH. Quality assessment was performed using the Joanna Briggs Institute Critical Appraisal Checklist for Case Reports. RESULTS: Of 783 identified records, 24 studies were included in the final analysis. Rituximab was typically administered at 375 mg/m2, with varying doses and treatment frequency. Clinical response, often seen within 1 month, was assessed by improvements in clinical symptoms and laboratory findings. Survival rates posttreatment displayed a wide range, with instances of complete remission and disease-free periods, as well as reports of relapse and mortality. CONCLUSION: Rituximab demonstrates the potential for significant clinical benefit in treating HLH, particularly when associated with EBV, showing promise in reducing disease activity and contributing to remission. These findings encourage further research and clinical trials to refine the therapeutic protocols and better understand the long-term effects of rituximab in HLH management.

Uncommon Manifestation: Thrombotic Thrombocytopenic Purpura Presenting Solely as Petechial Rash.

Thrombotic thrombocytopenic purpura (TTP) is a rare, life-threatening disorder typically presenting with a classic pentad of symptoms: thrombocytopenia, microangiopathic hemolytic anemia, neurological abnormalities, renal dysfunction, and fever. This report explores an unusual presentation of TTP in a 47-year-old female with a medical history of hypertension, hyperlipidemia, and chronic TTP, who exhibited only petechial rashes, generalized weakness, and headache. Notably, the petechial rash, a less common manifestation of TTP, became a pivotal clue for the diagnosis, underscoring the necessity for vigilance even when classic symptoms are absent. This case reinforces the imperative of a high suspicion index for TTP, especially in patients with thrombocytopenia and hemolytic anemia, irrespective of other traditional signs. Plasmapheresis remains the treatment cornerstone, removing autoantibodies and replenishing ADAMTS13, as evidenced by the patient's initial response. The administration of rituximab, targeting B cells to mitigate autoantibody production against ADAMTS13, featured prominently in her management, aligning with its recognized role in refractory or relapsing TTP cases. Despite an encouraging response to rituximab, a subsequent decline in platelet count indicated the unpredictable nature of TTP and the necessity for multi-pronged therapeutic strategies. The patient's medical background and persistently low ADAMTS13 levels hinted at a chronic relapsing trajectory associated with increased morbidity and mortality. This necessitates ongoing vigilance and treatment flexibility. Highlighting this atypical TTP presentation, the report calls for immediate, robust intervention, serving as a critical reminder of the heterogeneity of TTP manifestations and the complexities in its management, thereby contributing to broader clinical awareness and improved patient prognoses.

Successful Management of Atypical Hemolytic-Uremic Syndrome in Pregnancy Using Eculizumab: A Case Review.

Hemolytic-uremic syndrome (HUS) is a rare thrombotic microangiopathy characterized by the triad of microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and acute kidney injury. The disease is pathologically marked by fibrinoid necrosis within renal arterioles and glomerular capillaries. HUS can be categorized into typical variants, often linked to Shiga toxin-producing Escherichia coli (STEC) infection, and atypical variants that stem from dysregulation in the alternative complement pathway. Pregnancy is a recognized predisposing condition for HUS due to the potential reduction in complement regulatory proteins and the possibility of heightened maternal immune response. This report illustrates the case of a 36-year-old woman who, at 36 weeks of gestation, faced a breech presentation and was diagnosed with atypical HUS (aHUS) after placental abruption. Following a cesarean section, she developed complications, including a pelvic hematoma and bilateral hydronephrosis. Despite initial suboptimal response to plasmapheresis, the patient exhibited marked clinical improvement with eculizumab treatment, with no evidence of disease relapse.

Segmental Shielding: A Rare Case of Acute Respiratory Distress Syndrome with Middle Lobe Sparing.

Acute respiratory distress syndrome (ARDS) presents a formidable challenge in critical care, often resulting in high mortality rates, particularly in severe cases or those compounded by preexisting conditions. Despite substantial advancements in critical care, the heterogeneous nature of ARDS necessitates nuanced clinical approaches. ARDS is generally diagnosed through clinical evaluation, radiographic imaging, and laboratory tests, as well as acute onset, bilateral lung infiltrates on imaging, and a partial pressure of oxygen in arterial blood (PaO2)/fraction of inspiratory oxygen concentration (FiO2) ratio of less than 300 mmHg. Management involves measurements to improve oxygenation and provide mechanical ventilation to assist breathing. The typical manifestation of ARDS is diffuse lung involvement, which affects multiple lobes symmetrically. Here, we report an unusual case of ARDS in a 53-year-old female who was brought into the hospital in an unresponsive state, exhibiting hypoxic and hypotension requiring intubation. Subsequent imaging revealed a distinctive pattern: the preservation of the right middle lobe, diverging from the conventional diffuse pulmonary affliction. This case underscores the need for clinical vigilance and adaptability, as such atypical presentations can confound diagnosis and management, posing unique clinical challenges. This case highlights the importance of recognizing ARDS' diverse presentations. Moreover, understanding the mechanisms behind the lobar sparing could provide greater insight into the disease heterogeneity and guide tailored therapeutic approaches. The imperative for further research into these uncommon presentations is clear, as it may be vital to improving outcomes for a broader spectrum of ARDS patients.

Crushing Muscles: A Case Study on Rhabdomyolysis, Renal Failure, and Compartment Syndrome Triggered by Pre-Workout Supplement Abuse.

The use of steroids and protein-based dietary supplements for muscle enhancement is prevalent in contemporary society. While these products promise increased muscle mass and strength, they carry significant risks, including severe medical complications. The consumption of these supplements has been linked to adverse symptoms, including dehydration, gastrointestinal distress, dizziness, and alterations in heart rate and blood pressure, primarily due to ingredients like creatine, arginine, and caffeine. Following the proper dosage, ensuring adequate hydration, and consulting a healthcare provider to verify if the supplement's components could affect any pre-existing conditions is recommended. Indiscriminate use of these products, including taurine, can lead to serious side effects. We present a 36-year-old patient with severe rhabdomyolysis, life-threatening acid-base imbalance, renal and liver injury, and peripheral neuropathy associated with the use of performance-enhanced unregulated supplements and exercise. This case highlights the importance of recognizing and managing complications related to exercise-aid supplements, emphasizing early identification and management. Increasing social awareness and research on those products is highly needed to avoid supplement-associated complications and potential long-term disabilities.

Schwann Cell Hamartoma Presenting as a Colonic Polyp: A Rare Case Report With a Literature Review.

Mucosal Schwann cell hamartomas (MSCHs) are non-common noncancerous growths derived from Schwann cells in the peripheral nervous system, often found unexpectedly during routine colonoscopy examinations. These growths primarily occur in the colon, although they can also appear in the esophagus and are not linked to familial cancer syndromes. Diagnosis relies on specific histological characteristics and staining patterns. It is essential to distinguish MSCHs accurately since their appearance can closely resemble that of malignant tumors. Characteristically, these hamartomas test positive for S-100 protein but do not exhibit markers typical of other gastrointestinal growths, such as gastrointestinal stromal tumors (negative for KIT), leiomyomas (negative for smooth muscle actin), neurofibromas (negative for CD34), and perineuromas (negative for epithelial membrane antigen or claudin-1). This report discusses the case of a 48-year-old woman who was diagnosed with MSCH during a screening colonoscopy.

Hypercholesterolemia: a literature review on management using tafolecimab: a novel member of PCSK9 monoclonal antibodies.

Background: Cardiovascular diseases (CVD) persist as the leading cause of mortality globally, with atherosclerotic cardiovascular disease (ASCVD), including hypercholesterolaemia, being a significant contributor. Hyperlipidemia management includes various lipid-lowering drugs, including statins, Bempedoic acid, inclisiran, Lomitapide, ANGPTL3 inhibitors, and PCSK9 inhibitors. Statins have traditionally dominated lipid management therapies; however, a subset of patients remains unresponsive or intolerant to this therapy, necessitating novel therapeutic approaches. Tafolecimab, a promising and novel PCSK9 monoclonal antibody, demonstrated significant LDL-C reduction and a favourable safety profile in clinical trials. Objective: This review aimed to discuss the role and efficacy of Tafolecimab in the management of hypercholesterolaemia. Methods: The authors searched online databases, including PubMed, Scopus, and Embase, for articles related to talofecimab. Discussion: The efficacy of Tafolecimab in diverse patient populations, including those with comorbid conditions and various lipid disorders, has been explored. Ongoing trials, such as CREDIT-1, CREDIT-2, and CREDIT-4, have provided valuable insights into Tafolecimab's potential as a lipid-lowering agent. Moreover, the drug's extended dosing interval may enhance patient compliance and reduce treatment costs. It has also been found that Tafolecimab has more affinity for PCSK9 and a longer duration of LDL-C reduction than other monoclonal antibody drugs such as evolocumab. Thus, this review focuses on Tafolecimab, a novel PCSK9 monoclonal antibody, its mechanism of action, clinical trial outcomes, safety profile, and potential role in hypercholesterolaemia management. Despite its assuring potential, the long-term impact of Tafolecimab on cardiovascular outcomes remains to be fully elucidated, necessitating further research. Regulatory authorities like the FDA and EMA should also evaluate Tafolecimab's risks and benefits. Conclusion: In conclusion, Tafolecimab shows potential as an innovative therapeutic option for hypercholesterolaemia, particularly in patients with specific risk factors, but warrants additional research.

Cryptococcosis and Cryptococcal Meningitis: A Narrative Review and the Up-to-Date Management Approach.

Cryptococcosis is a fungal infectious disease that enormously impacts human health worldwide. Cryptococcal meningitis is the most severe disease caused by the fungus Cryptococcus, and can lead to death, if left untreated. Many patients develop resistance and progress to death even after treatment. It requires a prolonged treatment course in people with AIDS. This narrative review provides an evidence-based summary of the current treatment modalities and future trial options, including newer ones, namely, 18B7, T-2307, VT-1598, AR12, manogepix, and miltefosine. This review also evaluated the management and empiric treatment of cryptococcus meningitis. The disease can easily evade diagnosis with subacute presentation. Despite the severity of the disease, treatment options for cryptococcosis remain limited, and more research is needed.

Ceftriaxone-Induced Thrombotic Thrombocytopenic Purpura Treated Successfully With Plasmapheresis and Eculizumab: A Rare Case Report.

Thrombotic Thrombocytopenic Purpura (TTP) is a subtype of thrombotic microangiopathy (TMA) resulting in thrombocytopenia, anemia, fever, renal and neurological deficits. Although many drugs have been associated with drug-induced TTP, ceftriaxone has never been reported. Our case reports a patient who was started on ceftriaxone and developed TTP. Peripheral smear showed schistocytes and thrombocytopenia. Surprisingly, antibody formation against the metalloproteinase (ADAMTS13) levels were low-normal. The patient was treated with plasmapheresis and eczulimab, leading to platelet recovery and symptom resolution. TTP is a rare disorder and can be acquired or idiopathic. TTP can be diagnosed with normal ADAMTS13 as well. Further research is required to assess the mechanism by which ceftriaxone causes TTP. Physicians should consider the possibility of TTP in patients with similar presentations following ceftriaxone therapy and use it for timely diagnosis and treatment. Early diagnosis and treatment of ceftriaxone-induced TTP can prevent devastating consequences.

A Textbook Case of Human T-lymphotropic Virus-1 (HTLV-1)-Induced Adult T-cell Leukemia Treated With Cyclophosphamide, Hydroxydaunorubicin, Oncovin, and Prednisone/Prednisolone (CHOP).

Human T-lymphotropic virus-1 (HTLV-I) is an enveloped, single-stranded RNA virus of the Retroviridae family. The virus causes two well-recognized disease associations: adult T-cell leukemia/lymphoma (ATL) and HTLV-I-associated myelopathy (HAM), also known as tropical spastic paraparesis (TSP). We report a case of HTLV-1-induced adult T-cell lymphoma/leukemia in a 45-year-old female who presented with complaints of swelling on the right side of her neck and rash on her upper and lower extremities and abdomen. The patient also had a history of strongyloidiasis infection and Crohn's disease. She was found to have hypercalcemia and multiple lytic lesions of the bone found on the imaging. She also tested positive for HTLV-1 and T cell-positive for cluster of differentiation (CD) 2, CD3, partial CD5, and minimal CD56, later confirmed by the bone marrow (BM) and skin punch biopsies. ATL is characterized by the clonal proliferation of CD4+ T cells containing randomly integrated HTLV-I provirus, often associated with T-cell receptor gene rearrangements. ATL, in its aggressive forms, has one of the poorest prognoses of non-Hodgkin lymphoma. It is essential to raise awareness of ATL, although further research and trials are needed to solidify the treatment options to prevent mortality.

Necrotizing Autoimmune Myopathy: A Case Report on Statin-Induced Rhabdomyolysis.

Statin-induced necrotizing myopathy (SINM) is an uncommon but severe complication associated with statin medication. SINM can develop at any point after a person starts taking steroids. It is now being acknowledged as a component of the broader category of "statin-induced myopathy." Like other immune-mediated necrotizing muscle diseases, statin-induced myositis is identified by weakness in proximal muscles, increased serum creatine kinase (CK) levels, and, in some cases, dysphagia and respiratory distress. In addition, there is evidence of muscle cell damage when examined under a microscope, occurring with minimal or no infiltration of inflammatory cells. Diagnosing SINM promptly is frequently challenging due to its unpredictable development over time, with symptoms sometimes emerging many years after the initial exposure to statins. One distinctive characteristic of SINM is the continued presence of muscle inflammation and elevated CK levels even after discontinuing statin treatment. Currently, no clinical trials are available to guide how to manage statin-induced immune-mediated necrotizing myopathy (IMNM). Here, we present a case of a 42-year-old woman diagnosed with SINM and was found to have persistently elevated CPK despite discontinuation of statins. Our case also suggests that intravenous (IV) immunoglobins and steroids are an effective and well-tolerated alternative to immunosuppressants.

Clinical Conundrum of Acute Hepatitis B With Concurrent Hepatitis E Infection Leading to Severe Acute Liver Injury.

Acute liver injury in the setting of acute fulminant hepatitis caused by the hepatitis B virus (HBV) can occur both during primary infection and after chronic HBV reactivation. Guidelines recommend considering antiviral therapy in both cases. Antiviral therapy with a nucleoside analog may be beneficial in patients with acute liver failure from acute HBV infection, though not all studies have shown a benefit. This is a case of a 53-year-old woman with a past medical history of untreated hepatitis C with undetectable viral load and right breast cancer status post lumpectomy, who presented to the emergency department with complaints of yellowish skin and sclera discoloration with right upper quadrant pain for one week. She was a known intravenous drug abuser and binge alcohol user. Her labs were positive for hepatitis B, hepatitis E, and hepatitis C viruses. She also had elevated liver enzymes with hyperbilirubinemia showing severe acute liver injury. Computed tomography of the abdomen and pelvis with contrast was normal, and the abdominal ultrasound showed homogenous echotexture of the liver without a focal lesion. The patient was diagnosed with acute fulminant hepatitis B. After initial hemodynamic stabilization, N-acetylcysteine (NAC) and tenofovir were started, and transaminases were followed. Liver function tests showed a downtrend, and, in a few weeks, they came to baseline. Hepatitis B viral load became undetectable as well. Acute hepatitis B infection is seldom treated. The presented case depicts the use of tenofovir in the setting of severe acute liver injury due to hepatitis B. Starting antiviral therapy (especially tenofovir disoproxil fumarate) early in the disease course was shown to have very assuring results with complete resolution of symptoms and normalization of liver function tests. The treatment protocol for acute HBV deserves further investigation.

Hashimoto's Thyroiditis Encephalopathy Induced by COVID-19 Infection.

Various factors can lead to thyroiditis, including any acute inflammatory process, especially viral illness. While coronavirus disease 2019 (COVID-19) has been linked to disorders of various systems, there is a lack of literature showing an association of coronavirus with the cause of Hashimoto's thyroiditis. Several possible mechanisms for this outcome have been proposed; chief among them is molecular mimicry. Here, we are reporting a case of Hashimoto's thyroiditis incited by COVID-19 in a 34-year-old obese female who presented with anxiety, behavioral changes, and repeated head movements. The patient had an elevated thyroid stimulating hormone (TSH) level, a low thyroxine (T4) level, and a positive anti-microsomal antibody screen. The patient also tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. Ultrasound of the patient's neck showed an enlarged heterogeneous thyroid gland. Thyroid replacement therapy with intravenous levothyroxine was started with the subsequent oral transition. Concurrently, she received antibiotics, steroids, and low-molecular-weight heparin for COVID-19. The patient exhibited significant improvement in her mental status, with an eventual return to baseline. The results of the thyroid panel obtained at the outpatient follow-up were normal. Although there is a paucity of data to show COVID-19 as a cause of this painless thyroiditis, this case demonstrates such causality between these two.

A Case Report of Wernicke's Encephalopathy Disguised As Limbic Encephalitis: A Clinical Puzzle.

Wernicke's encephalopathy (WE) is the presence of neurological symptoms in the central nervous system caused by thiamine (Vitamin B1) deficiency. It is an acute clinical condition characterized by confusion, ataxia, and ophthalmoplegia triad. WE is most commonly observed in chronic alcohol users, while it can also present in non-alcoholics. We present a 33-year-old man with alcohol-induced WE who presented with altered mental status and fever. His initial diagnosis was skewed towards bacterial meningitis and limbic encephalitis, but MRI findings were consistent with WE. The patient responded promptly to intravenous (IV) thiamine infusion, and his mental status changed significantly. Repeat EEG in 15 days shows complete recovery with normal brain wave activity. Untreated WE is a significant cause of permanent neurological morbidity and mortality, easily preventable. High suspicion of WE should always be entertained, especially when patients have a known history of alcohol use. Early initiation of IV thiamine could prevent the consequences. Hence, it is essential to raise awareness of WE to take measures without delay and reduce mortality and morbidity with an improved prognosis.

Ophthalmoparesis and Bilateral Ptosis as a Rare Manifestation of Todd's Phenomenon: Case Report and Review.

Todd's paresis or phenomenon (TP) is a focal weakness in a part of the body after a seizure. Seizure is an abrupt change in behavior caused by the cerebral cortex's electrical hyper-synchronization of neuronal networks. After the seizure, there is usually a transition period from the ictal state to the pre-seizure baseline level of awareness and function, referred to as the postictal period. Postictal symptoms include many systems, including sensory, motor, and psychosis. This phenomenon is named after Robert Bentley Todd, who first described it. Todd's paresis can be confused with other conditions, most commonly a stroke. Postictal ocular manifestation may be accompanied by aphasia or hemiplegia, but isolated gaze palsy is rarely reported. We are reporting a rare and first known isolated ophthalmoparesis and ptosis as postictal findings with no structural abnormalities present in imaging studies and complete resolution over three weeks on its own as an atypical postictal phenomenon. Patients with an underlying structural abnormality of the brain are more susceptible to Todd's phenomenon. Unusual manifestations of Todd's phenomenon are rare but clinically relevant and are decisive in therapeutic decision-making. Our patient presents a rare manifestation of Todd's phenomenon as ptosis and ophthalmoparesis in an elderly male with no underlying structural brain abnormalities that resolved within three weeks. Further research into the causes is needed to distinguish it from a stroke.