Human T-cell Lymphotropic Virus Type 1 (HTLV-1)-Associated Adult T-cell Leukemia/Lymphoma in a Patient Previously Treated for Strongyloidiasis.

Adult T-cell leukemia/lymphoma (ATLL) is a rare form of T-cell lymphoma with poor median survival time and limited response to chemotherapy. We present a 45-year-old female from Ghana with generalized body rash, hypercalcemia, lymphadenopathy, and lytic bone lesions. She had a history of strongyloidiasis, treated two years ago, and her serology was positive for the human T-cell lymphotropic virus type 1 (HTLV-1). Histopathology of cervical lymph node and abdominal rash biopsy revealed T-cell lymphoma. We present a literature review on the topic and the challenges of diagnosis. We emphasize the importance of considering HTLV-1-associated ATLL in patients who have been treated for strongyloidiasis in the past and are presenting with rash or lymphadenopathy.

Efficacy and Safety of RET-Specific Kinase Inhibitors in RET-Altered Cancers: A Systematic Review.

RET proto-oncogene encodes receptor tyrosine kinase. Selpercatinib and pralsetinib are the only RET-specific tyrosine kinase inhibitors approved by FDA in RET-altered tumors. We searched PubMed, Embase, Cochrane, WOS, and Clinicaltrials.gov. Objective-response, complete-response, and partial-response were 60-89%, 0-11%, and 55-89%, respectively, with the use of RET-specific drugs. ≥Grade 3 adverse events were seen in 28-53% of the patients, with hypertension, change in ALT, QT prolongation, neutropenia, and pneumonitis among the common side effects. Hence, selpercatinib and pralsetinib were effective and well tolerated by most of the patients with RET-altered tumors.

From Euphoria to Emergency: Exploring the Role of K2/Spice in Diffuse Alveolar Hemorrhage.

Marijuana or cannabis has been one of the most widely used recreational drugs, in the United States. However, a sinister counterpart has emerged in recent times: K2/Spice, a synthetic rendition of tetrahydrocannabinol (THC), capturing increasing popularity. Alarming reports have linked this synthetic compound to a multitude of life-threatening complications, ranging from acute kidney injury (AKI) from direct nephrotoxicity to cardiac arrest. Here we present the case of a 34-year-old man who presented with hemoptysis, later found to have diffuse alveolar hemorrhage (DAH) on the investigation after smoking K2/Spice successfully treated with a course of intravenous steroids. The case presented underscores the urgent need for increased awareness about the potential complications associated with synthetic compounds like K2/Spice, such as diffuse alveolar hemorrhage, and the importance of developing effective treatment strategies.

A Rare Case of Kikuchi-Fujimoto Disease.

Kikuchi-Fujimoto disease (KFD) is an autoimmune condition that is more common in females and occurs in the third decade of life. The condition is usually benign and self-resolving and is characterized by fever, cervical lymphadenopathy, night sweats, myalgia, and rashes. The disease can be misdiagnosed as reactive follicular hyperplasia, tuberculous lymphadenitis, systemic lupus erythematosus, and malignant lymphoma. The diagnosis of KFD involves the excision of the affected lymph node. Although there is no specific treatment for the disease, usually symptomatic and supportive measures are effective; however, steroids and immunosuppressive therapies are considered in more severe cases. The disease lasts for around one to four months. The neurological complications include cerebellar ataxia, meningoencephalitis, and aseptic meningitis. Here, we describe the case of a 36-year-old male who presented with complaints of fever, malaise chills, anorexia, and fatigue associated with a tender right axillary lymph node. The patient underwent a biopsy which confirmed KFD and responded well to supportive therapy.

Efficacy and safety of antibody-drug conjugates in triple-negative and HER-2 positive breast cancer: A systematic review and meta-analysis of clinical trials.

Breast cancer (BC) is the 2nd most common cause of cancer-related deaths. Antibody-drug conjugates (ADCs) are monoclonal antibodies linked to cytotoxic agents and are directed towards a specific tumor protein. Therefore, they are more potent and can have relatively less toxicity. In this meta-analysis, we assessed the efficacy and safety of ADCs in breast cancer. We searched PubMed, Cochrane, Web of Science, and clinicaltrials.gov for relevant studies and included 7 randomized clinical trials (N = 5,302) and 7 non-randomized clinical trials (N = 658). R programming language software was used to conduct this meta-analysis. In 4 RCTs on HER-2 positive BC (N = 2,825), the pooled HR of PFS and OS was 0.72 (95% CI = 0.61-0.84, I2 = 71%) and 0.73 (95% CI = 0.64-0.84, I2 = 20%), respectively in favor of ADCs versus chemotherapy. In RCT on triple negative BC (N = 468), HR of PFS and OS were 0.55 (95%CI = 0.51-0.61) and 0.59 (95% CI = 0.54-0.66), respectively, in favor of saci-gov versus chemotherapy. In RCT on HER-2 positive residual invasive BC, HR of recurrence/death was 0.61 (95% CI = 0.54-0.69) in favor of ADC versus chemotherapy. In an RCT (N = 524), the HR of PFS and OS were 0.28 (95% CI = 0.22-0.37) and 0.55 (95%CI = 0.36-0.86), respectively, in favor of trastuzumab-deruxtecan (T-der) as compared to trastuzumab-emtansine (T-DM1). Anemia, rash, diarrhea, fatigue, hypertension, thrombocytopenia, and elevated aminotransferases were the common ≥grade 3 adverse events reported in 4%, 1%, 2%, 1%, 2%, 9%, and 3% of the patients, respectively. ADCs were more effective than single and double agent chemotherapy in patients with HER-2 positive or triple negative BC. Among ADCs, T-der was more effective than T-DM1.

Small Bowel Enteritis and Myocardial Depression Complicating Organophosphorus Poison in a Patient With Sleeve Gastrectomy and Intestinal Bypass Surgeries: An Atypical Presentation.

Organophosphate (OP) is a pesticide that has been used in agriculture and domestic pest control since the mid-1900s. Acute OP toxicity is caused by inhibiting the acetylcholinesterase (AChE) enzyme, resulting in a cholinergic surge. It is treated with atropine and pralidoxime. Our case is a patient with a past history of sleeve gastrectomy and intestinal bypass surgery presented after oral OP intake. He initially had small bowel enteritis, followed by lactic acidosis, acute renal injury, and distributive shock. The serum troponin had peaked 50-folds. The echocardiography showed myocardial depression and global hypokinesia with no significant wall motion abnormalities. In contrast to classic bradycardia with OP poisoning, our patient developed persistent sinus tachycardia on the second day. He had a concomitant alcohol withdrawal syndrome, which was managed with intravenous (IV) hydration and benzodiazepines. He had a dramatic improvement on the third day with near resolution of creatinine and lactic acid. The outpatient cardiac follow-up showed partial resolution of the left ventricular ejection fraction (EF) to 48%. In this literature, we discuss the complications and long-term effects of bariatric surgeries, particularly on gastric emptying and medication absorption. We also discuss OP mechanism of action, clinical presentation, therapeutic lines, and atypical presentations in the prior literatures.

Safety and Efficacy of Tyrosine Kinase Inhibitors in Immune Thrombocytopenic Purpura: A Systematic Review of Clinical Trials.

Immune thrombocytopenic purpura (ITP) is an acquired antibody or cell-mediated platelet damage or decreased platelet production. Steroids, IV immunoglobulins (IVIG), and Rho-anti-D antibodies are the commonly used initial treatments for ITP. However, many ITP patients either do not respond or do not maintain a response to initial therapy. Splenectomy, rituximab, and thrombomimetics are the commonly used second-line treatment. More treatment options include tyrosine kinases inhibitors (TKI), including spleen tyrosine kinase (Syk) and Bruton's tyrosine kinase (BTK) inhibitors. This review aims to assess the safety and efficacy of TKIs. Methods: Literature was searched on PubMed, Embase, WOS, and clinicaltrials.gov using keywords, "tyrosine kinase" and "idiopathic thrombocytopenic purpura". PRISMA guidelines were followed. Results: In total, 4 clinical trials were included with 255 adult patients with relapsed/refractory ITP. In all, 101 (39.6%) patients were treated with fostamatinib, 60 (23%) patients with rilzabrutinib, and 34 (13%) with HMPL-523. Patients treated with fostamatinib achieved a stable response (SR) and overall response (OR) in 18/101 (17.8%) and 43/101 (42.5%) of the patients, respectively, while SR and OR were achieved in 1/49 (2%) and 7/49 (14%) of the patients, respectively, in the placebo group. Patients treated with HMPL-523 (300 mg dose expansion) achieved an SR and OR in 5/20 (25%) and 11/20 (55%) of the patients, respectively, while SR and OR were achieved in 1/11 (9%) of the patients treated with the placebo. Patients treated with rilzabrutinib achieved an SR in 17/60 (28%) patients. Dizziness (1%), hypertension (2%), diarrhea (1%), and neutropenia (1%) were serious adverse events in fostamatinib patients. Rilzabrutinib or HMPL-523 patients did not require a dose reduction due to drug-related adverse effects. Conclusions: Rilzabrutinib, fostamatinib, and HMPL-523 were safe and effective in the treatment of relapsed/refractory ITP.

Efficacy and Safety of Recombinant Thrombomodulin for the Prophylaxis of Veno-Occlusive Complication in Allogeneiccit Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.

BACKGROUND: Hepatic veno-occlusive disease (VOD), also termed as sinusoidal obstruction syndrome (SOS), is a lethal complication after hematopoietic stem cell transplantation (HSCT). Various factors put patients undergoing allogeneic HSCT at an increased risk for VOD. Thrombomodulin (TM) is an important factor which has a wide range of effects, including anticoagulant, anti-inflammatory, angiogenic, and protective effect, on endothelial cells. It plays a role in preventing excessive coagulation and thrombosis by binding with thrombin and inhibiting the coagulation cascade. There are a limited number of options for the prevention of this fatal complication. Recombinant thrombomodulin (rTM), an endothelial anticoagulant co-factor, as prophylactic therapy might be able to prevent veno-occlusive complications after stem cell transplantation. METHODS: A literature search was performed on PubMed, Embase, and Web of Science. We used the following Mesh terms and Emtree terms, "Hepatic Veno-Occlusive Diseases" OR "Sinusoidal Obstruction" OR "Stem Cell Transplantations " AND "Thrombomodulin" from the inception of data up to April 1, 2021. The PICO (Patient/Population, Intervention, Comparison and Outcomes) framework was used for the literature search. RESULTS: For the VOD incidence after HSCTstem cell transplantation, the result was in favor of rTM with a risk ratio (RR) of 0.53 (I2 = 0%, 95% confidence interval [CI] = 0.32-0.89). The incidence of transplant-associated thrombotic microangiopathy (TA-TMA) after HSCT was reduced in rTM group. The RR for incidence of TA-TMA was 0.48 (I2 = 62%, 95% CI = 0.20-1.17) favoring rTM. The RR for incidence of graft-versus-host disease (GvHD) was also lower in rTM group, 0.48 (I2 = 64%, 95% CI = 0.32-0.72). CONCLUSION: In our meta-analysis, we evaluate the efficacy and safety of rTM in the prevention of SOS after HSCT. According to our results, rTM use led to a significant reduction in SOS episodes, TA-TMA, and GvHD after HSCT.

A Case of Malignant Pleural Effusion Secondary to Endometrial Cancer After One Year of Hysterectomy.

Endometrial cancer is the most common malignant tumor of the female genital tract. It can rarely metastasize to the lung, presenting as a pulmonary nodule and pleural effusion. Here we present a case of a 76-year-old female with a history of endometrial cancer who underwent a total abdominal hysterectomy and came one year later for evaluation of shortness of breath. She was found to have pleural effusion. Diagnostic and therapeutic thoracentesis was positive for malignant cells originating from endometrial cancer. The patient could not tolerate chemotherapy due to poor functional status, and a tunnel pleural catheter was placed for symptomatic relief. In conclusion, it is a rare finding of malignant pleural effusion to have an origin as endometrial cancer. Pleura is the rare distant site of involvement from endometrial cancer.

Efficacy and toxicity of surufatinib in neuroendocrine tumors: A systematic review and meta-analysis.

The incidence and prevalence of neuroendocrine neoplasms (NENs) has increased in the US in recent decades. These are well-vascularized tumors, but no antiangiogenic drug has been approved for treatment of extra-pancreatic NENs. The aim is to assess efficacy and safety of surufatinib in pancreatic and extra-pancreatic NETs. We searched PubMed, Embase, Cochrane Library, Web of Science and Clinicaltrials.gov. Clinical trials and observational studies that provided safety and efficacy data in clinical terms were included. Characteristics of the study, baseline characteristics of participants, treatment drugs, measures of efficacy, and toxicity (≥grade 3 adverse effects) were extracted. The meta-analysis was performed using the "R" programming language. Risk ratio (RR) of objective response (OR)/partial response (PR) was 8.55 (95% CI: 1.68-43.66, I2  = 0) in favor of surufatinib. The hazard ratio (HR) of progression-free survival (PFS) was 0.48 (95% CI: 0.25-0.92, I2  = 77%) in favor of surufatinib. The risk of ≥grade 3 adverse effects: diarrhea, hypertension, hypertriglyceridemia, proteinuria, and vomiting were high with the use of surufatinib. Quality of life (QoL) was similar in surufatinib and placebo groups except for the diarrhea that was high with surufatinib. Lack of randomized clinical trials in non-Chinese population. Surufatinib is well tolerated and is more effective than placebo in both pancreatic and extra-pancreatic NETs. More multicenter randomized, double-blinded clinical trials are needed to confirm these results.

Efficacy and Safety of Fevipiprant in Asthma: A Review and Meta-Analysis.

Fevipiprant is a non-steroidal oral prostaglandin D2 (PGD2) receptor 2 antagonist that reduces bronchial wall inflammation, possibly improving clinical outcomes in the asthmatic population. A systemic review search was conducted on PubMed, Embase, and Central Cochrane Registry. Randomized clinical trials were included with Fevipiprant as an intervention arm compared to placebo. For continuous variables, the standardized mean difference, and for discrete variables, Mantel-Haenszel Risk Ratio (MH Risk ratio) was used for analysis. Confidence interval of 95% and p-value < 0.05 was considered significant. The analysis was done using a random-effects model irrespective of heterogeneity. Heterogeneity was evaluated using the I2 statistic. A total of five articles, including seven trials, were included in the analysis. There was significant increase in post-bronchodilator forced expiratory volume in one second (FEV1) 0.249 (0.157-0.341), p<0.001 and pre-bronchodilator FEV1 0.115 (0.043 to 0.188), p=0.002. A decrease in asthma control questionnaire (ACQ) score of -0.124 (-0.187 to -0.062), p<0.001, was reported. Statistically significant asthma exacerbation reduction was reported in the high eosinophil count population with a daily dose of 450mg 0.77 relative risks (RR) (0.61-0.97). There was a positive deviation toward Fevipiprant 450mg dose for asthma reduction in the overall population, but it was not statistically significant. Fevipiprant produced a slight statistically significant reduction in asthma exacerbations in the high eosinophil count population with favorable deviation in the overall population. It significantly increased pre-and post-bronchodilator FEV1 and improved ACQ scores in treated patients. The benefits, though statistically significant, failed to translate into clinical importance.

Current Status of Monoclonal Antibodies-Based Therapies in Castration-Resistant Prostate Cancer: A Systematic Review and Meta-Analysis of Clinical Trials.

Background Multiple patients with prostate cancer become resistant to castration therapies, which is termed castration-resistant prostate cancer (CRPC). Purpose The purpose of this review is to assess the status of efficacy (≥50% decline in prostate-specific antigen (PSA), progression-free survival (PFS), and overall survival (OS)) and safety (grade 3-4 adverse effects) of monoclonal antibodies in CRPC. Data source We searched databases including PubMed, Embase, Cochrane, Web of Science, and ClinicalTrials.gov. Results Hazard ratios of PFS and OS were 0.77 (95% CI = 0.69-0.87, I2 = 53%) and 0.98 (95% CI = 0.86-1.11, I2 = 40%), respectively, in the favor of monoclonal antibodies as compared to placebo. Risk ratio (RR) of >50% decline in PSA was 1.99 (95% CI = 0.97-4.08, I2 = 53%) in favor of monoclonal antibodies. Pooled incidence of >50% decline in PSA levels was 15% (95% CI = 0.1-0.23, I2 = 83%), 29% (95% CI = 0.14-0.51, I2 = 93%), 63% (95% CI = 0.49-0.76, I2 = 77%), and 88% (95% CI = 0.81-0.93, I2 = 0%) in single, two, three, and four-drug regimens, respectively. Conclusion Monoclonal antibodies are well tolerated and showed better PFS as compared to placebo. However, OS was only improved with ipilimumab. Denosumab delayed skeletal-related adverse events as compared to zoledronic acid. More multicenter double-blind clinical trials may be needed to confirm these results.

Comparison of normal saline solution with low-chloride solutions in renal transplants: a meta-analysis.

BACKGROUND: Normal saline solution (NSS) has been the fluid of choice for renal transplant patients, but it can lead to hyperchloremic acidosis and hyperkalemia. This study was performed to compare the safety profile of low-chloride solutions with that of NSS in renal transplant patients. METHODS: We conducted a systemic review search on PubMed, Embase, and the Central Cochrane Registry. Randomized clinical trials (RCTs) and matched cohort studies involving NSS as the control arm and low-chloride solutions as an intervention arm were chosen. The standardized mean difference for continuous variables, the odds ratio (OR) for discrete variables, and a 95% confidence interval (CI) for effect sizes were used. A p-value of <0.05 was considered statistically significant. Analysis was performed using a random-effects model irrespective of heterogeneity, which was evaluated using I2 statistics. RESULTS: Nine RCTs and one cohort study with a total of 726 patients were included. After transplantation, serum potassium was significantly lower in the low-chloride group (standardized mean difference compared to NSS group, -0.38 mEq/L; 95% CI, -0.66 to -0.11; p = 0.007). Similarly, postoperative chloride was lower in the low-chloride group (-2.41 mEq/L [-3.34 to -1.48], p < 0.001). No statistically significance was observed in delayed graft function (OR, 0.98 [0.56-1.69], p = 0.93), day 3 creatinine (-0.14 mg/dL [-0.46 to 0.18], p = 0.38), or day 7 urine output (-0.08 L [-0.29 to 0.12], p = 0.43). CONCLUSION: Use of NSS during renal transplant leads to increased incidence of hyperchloremic acidosis with subsequent hyperkalemia, but clinical significance in the form of delayed graft function or postoperative creatinine remains comparable to that of low-chloride solutions.

Case report of peritoneal carcinomatosis of plasma cell origin in a patient with newly diagnosed HIV: A terminal event.

BACKGROUND: B-cell tumors and plasma cell malignancies have been identified in persons living with the human immunodeficiency virus (PLHIV). The literature review has revealed numerous reports of solitary plasmacytomas with metastasis in PLHIV. CASE REPORT: A young patient with no prior medical or surgical history presented with tumor lysis syndrome secondary to metastatic plasma cell Epstein-Baer virus (EBV) related malignancy with peritoneal carcinomatosis. The history and clinical picture promptly led to the diagnosis of HIV. The subsequent hospital course was dismal, and lifespan was cut short by multi-organ failure. CONCLUSION: This case is being reported to highlight the suspicion of HIV in patients presenting acutely with aggressive plasma cell malignancies.

Systematic Review and Meta-analysis of CD19-Specific CAR-T Cell Therapy in Relapsed/Refractory Acute Lymphoblastic Leukemia in the Pediatric and Young Adult Population: Safety and Efficacy Outcomes.

Acute lymphoblastic leukemia (ALL) typically responds better when treated with multiagent chemotherapy in the pediatric and young adolescent populations. Treatment of relapsed/refractory (RR) ALL remains a challenge. Even after stem-cell transplantation and intensive chemotherapy, the prognosis of RR-ALL remains grave. The advent of chimeric antigen receptors has demonstrated promising results in RR-ALL. Chimeric antigen receptor-modified T cells (CAR-T) and engineered T cells are used to target cancer cells. In 2017, the US Food and Drug Administration approved CD19-specific CAR-T (tisagenlecleucel) therapy for RR-B-cell ALL in patients under 25 years old. In this systematic review, we discuss the efficacy and safety of CD19-specific CAR-T therapy in RR-B-cell ALL in the pediatric and young adult population. We searched the PubMed, Embase, Web of Science, Cochrane Library, and clinical trials databases. A total of 448 patients received a CD19-specific CAR-T product, and 446 patients had evaluable data. The age range was 0 to 30 years. The incidence rate of complete remission was 82%. The cumulative incidence of relapse after CD19-specific CAR-T therapy is 36%. Similarly, the incidence rate of grade 3 or higher adverse events of neutropenia, thrombocytopenia, neurotoxicity, infections, and cytokine release syndrome were 38%, 23%, 18%, 29%, and 19%, respectively. Our subgroup analysis shows the incidence rate of minimal residual negative complete remission was 69% with the CD28z costimulatory domain, 81% with the 4-1BB domain, and 77% with fourth-generation CD19-specific CAR-T therapy.

CAR T Cell Therapy in Pancreaticobiliary Cancers: a Focused Review of Clinical Data.

OBJECTIVE: CAR T cell therapy is an innovative approach to treat cancers in the modern era. It utilizes the application of chimeric antigen receptors targeted against specific antigens expressed by the tumor cells. Although its efficacy is established in hematological malignancies, the safety and efficacy of this therapy in solid tumors, especially pancreaticobiliary cancers, is a highly investigated aspect. A focused review of clinical data was conducted to examine the outcomes of this therapy in pancreaticobiliary cancers. METHODS: A comprehensive literature search was done on Medline and Embase databases through April 24, 2020 for studies that evaluated the outcomes of CAR T cell therapy in pancreaticobiliary cancers. RESULTS: There were six phase 1 trials, while one was phase 1/2. Some of these trials were specifically done for pancreaticobiliary cancers, while others included patients of various solid organ cancers, including pancreatic and biliary tract cancers. The target antigens for therapy in these trials included mesothelin, CD133, prostate stem cell antigen, claudin 18.2, epidermal growth factor receptor, and human epidermal growth factor receptor 2. CAR T cell therapy has shown very few grade 3 and 4 side effects. Most of the adverse events are associated with cytokine release syndrome. CONCLUSION: CAR T cell therapy has a manageable safety profile based on phase 1 studies, and efficacy assessments are currently ongoing in dose expansion and phase 2 studies.

Efficacy and safety of recently approved drugs for sickle cell disease: a review of clinical trials.

Sickle cell disease is prevalent in several parts of the world. Most hospitalizations of these patients are related to pain crisis episodes. Moreover, levels of hemoglobin are lower in sickle cell disease patients as compared with the general population. Complications related to sickle cell disease are managed with blood transfusions, hydroxyurea, and opioids. Despite these therapies, patients with sickle cell disease experience multiple pain crisis episodes leading to hospitalizations and end-organ damage. The US Food and Drug Administration has approved three new drugs-L-glutamine, voxelotor, and crizanlizumab-for the prophylaxis and treatment of complications related to sickle cell disease. This review was aimed at assessing the efficacy and safety of recently approved drugs for the treatment of sickle cell disease. A comprehensive search was made on PubMed and clinicaltrials.gov to look for clinical trials reporting the efficacy and safety of recently approved drugs for sickle cell disease. Based on the results of clinical trials, L-glutamine, voxelotor, and crizanlizumab were well tolerated by sickle cell disease patients. L-Glutamine and crizanlizumab reduced the number of sickle cell crisis episodes, while voxelotor improved the level of hemoglobin in sickle cell disease patients. These drugs were effective alone and in combination with hydroxyurea.