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Competing Interests: Declaration of interests We declare no competing interests.

Background: Hepatic encephalopathy (HE) is defined as brain dysfunction that occurs because of acute liver failure or liver cirrhosis and is associated with significant morbidity and mortality. Lactulose is the standard of care till this date; however, polyethylene glycol (PEG) has gained the attention of multiple investigators., Methods: We screened five databases namely PubMed, Scopus, Web of Science, Cochrane Library and Embase from inception to 10 February 2021. Dichotomous and continuous data were analysed using the Mantel-Haenszel and inverse variance methods, respectively, which yielded a meta-analysis comparing PEG versus lactulose in the treatment of HE., Results: Four trials with 229 patients were included. Compared with lactulose, the pooled effect size demonstrated a significantly lower average HE Scoring Algorithm (HESA) Score at 24 hours (Mean difference (MD)=-0.68, 95% CI (-1.05 to -0.31), p<0.001), a higher proportion of patients with reduction of HESA Score by ≥1 grade at 24 hours (risk ratio (RR)=1.40, 95% CI (1.17 to 1.67), p<0.001), a higher proportion of patients with a HESA Score of grade 0 at 24 hours (RR=4.33, 95% CI (2.27 to 8.28), p<0.0010) and a shorter time to resolution of HE group (MD=-1.45, 95% CI (-1.72 to -1.18), p<0.001) in favour of patients treated with PEG., Conclusion: PEG leads to a higher drop in the HESA Score and thus leads to a faster resolution of HE compared with lactulose., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

There has been a high incidence of thromboembolic diseases in patients with coronavirus disease 2019 (COVID-19) pneumonia. We present a case of a healthy 32-year-old male with no past medical history who presented with shortness of breath, tested positive for COVID-19, and was found to have a large acute saddle pulmonary embolism., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Hoilat et al.)

Bouveret syndrome is the rarest variant of gallstone ileus, with a high morbidity and mortality rate as well as life-threatening complications. We present a case of an 86-year-old woman who presented with abdominal pain and was diagnosed with acute cholecystitis. After laparoscopic cholecystectomy, her symptoms did not improve. She then underwent endoscopic retrograde cholangiopancreatography and was found to have a stone causing duodenal bulb obstruction. The stone was removed using a snare, and her symptoms improved greatly. This rare case of Bouveret syndrome with no apparent fistula was successfully treated using endoscopic measures., (Copyright © 2020 Baylor University Medical Center.)

The practice of choosing the next best therapy for patients with relapsed and/or refractory multiple myeloma (RRMM) is becoming increasingly complex. There is no clear consensus regarding the best treatment sequence for RRMM. With the approval of novel proteasome inhibitors (ixazomib and carfilzomib), immunomodulatory agents (pomalidomide), monoclonal antibodies (daratumumab and elotuzumab), and other targeted therapies, multiple combination regimens utilizing these agents are being studied with the goal of enhancing disease control, prolonging progression-free survival, and improving overall survival. We, herein, describe a review of FDA-approved regimens for RRMM patients and offer a paradigm in selecting subsequent treatment regimens, focusing on patient specific morbidity, treatment toxicity, and disease-specific characteristics., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

The testicular seminomas are germ-cell tumors which account for approximately 50% of all testicular tumors. Most primary testicular germ cell tumors metastasize through a lymphatic system in a predictable pattern with the retroperitoneal lymph nodes being the most common initial metastatic site. Hematological metastasis to the distant organs is less common, and except for pulmonary metastasis, changes the classification from good to intermediate prognosis. Metastasis of testicular seminoma to the prostate is an extremely rare entity with only five reported cases in the literature. In this report, we present a 63-year-old male with recurrent testicular seminoma presenting in prostate., (© 2019 The Authors.)

Chilaiditi's sign refers to the interposition of the colon (usually the transverse colon) between the diaphragm and the liver. When associated with abdominal pain it is referred to as Chilaiditi's syndrome. Chilaiditi's sign is rare entity with an estimated incidence of 0.025 to 0.28% worldwide. The sign occurs more frequently in males, with a male to female ratio of 4:1. Apparent pneumoperitoneum seen on imaging below the right hemidiaphragm, a life-threatening condition, may in fact be merely Chilaiditi's sign. Awareness of this phenomenon and its consideration as a differential diagnosis is essential to prevent unnecessary laparoscopic intervention. Here we present a case of a 74-year-old male who was incidentally found to have free air under the diaphragm without symptoms of abdominal pain. After further evaluation by the radiologists and surgeons it was concluded that he had Chilaiditi's sign and no further intervention was required. However, due to the lack of awareness of this radiographic finding patients can be subjected to unnecessary surgical intervention., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2019, Sohal et al.)

[This retracts the article DOI: 10.7759/cureus.4639.]., Competing Interests: No competing interests declared.

Problem-based learning is a learner-centered teaching method, which uses real-world scenarios to promote student learning of concepts and principles. The aim of our study is to analyze the consequence of increased problem difficulty on team-based learning and the analytical skills of medical students. In our prospective descriptive study, two problem-based learning scenarios prepared on the topic of hypercortisolism were given to 197 students in two successive sessions. At the end of two sessions, the perceptions of students about team-based learning were documented using a five-point Likert scale on a standardized questionnaire for both scenarios (simple and complex) simultaneously. A written test consisting of multiple-choice questions (MCQs) and short essay questions (SEQs) was given at the end of a complex scenario to test the problem-solving skills and retention of knowledge. No statistically significant difference (p> 0.05) was noted in team-based learning between the simple and complex problem-based learning scenario. MCQs and SEQs of C-2 (interpretation) level were attempted well than C-1 (recall) level and C3 (problem-solving) level. In conclusion, the understanding of the problem by the medical students was improved; however, there was no significant improvement in the problem-solving skills and knowledge retention of the students., Competing Interests: The authors have declared that no competing interests exist.

Blinatumomab and donor lymphocyte infusion (DLI) combination is a promising cancer therapy, whereby blinatumomab might achieve an initial reduction in leukemic-cell burden using T cells, and after tumor clearance, DLI can potentially stimulate the donor immune system to achieve longer lasting remission. Here, we present a 51-year-old female with mixed phenotype acute leukemia who had a hematologic relapse 3 months after she received total body irradiation-based myeloablative allogeneic hematopoietic stem cell transplantation from an unrelated human leukocyte antigen matched (10/10) donor and achieved complete remission with minimal residual disease negativity by multi-parameter flow cytometry using the combination of blinatumomab and DLI. To the best of our knowledge, this is the first report to describe the use of blinatumomab and DLI combination therapy in the treatment of B/myeloid mixed phenotype acute leukemia.

The current practice for diagnosing graft versus host disease (GVHD) includes clinical or endoscopic evaluation of the patient. Clinical diagnosis is limited by an overlapping symptomatic spectrum with infectious causes, a common scenario in the post-transplant setting where an invasive procedure, such as endoscopy, is often impractical. We, therefore, evaluated the role of fecal calprotectin as a diagnostic as well as a prognostic biomarker for gastrointestinal GVHD (GI-GVHD) occurrence and severity in the post-hematopoietic transplant population. Following Prisma guidelines, we performed a systematic search of articles published after 2004 using the PubMed, Embase, Cochrane Library, and Web of Science databases. After a detailed screening, 10 studies involving a total of 494 patients were included. In the cohorts comparing median fecal calprotectin (mFC) level in GI-GVHD vs. non-GI-GVHD patients, the results indicated an increase in the mFC level in patients with GI-GVHD when compared to non-GI-GVHD patients. Similarly, an increase in the mFC level was seen in accordance with the severity of the disease. Moreover, corticosteroid-resistant patients had a higher mFC level as compared to corticosteroid-sensitive patients. Our study indicates that the mFC level can be used for diagnosing as well as predicting the treatment response to GI-GVHD. However, future randomized prospective trials involving larger populations are needed to further explore its significance., Competing Interests: The authors have declared that no competing interests exist.

Investigators are using checkpoint inhibitors (CPIs) to treat aggressive hematologic malignancies in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) and in some patients with relapsed disease after allo-HSCT. CTLA-4 inhibitors and PD-1 inhibitors are 2 main types of CPIs, which work through activation of the immune system. On one hand, CPIs can achieve graft-versus-tumor effect, and on the other hand, there is a risk of graft-versus-host disease (GVHD). After a comprehensive literature review, we included data (n = 283) from 24 studies (11 original manuscripts and 13 case reports or case series) and evaluated the results to assess the safety and efficacy of CPI use in conjunction with allo-HSCT. Among the 283 patients, 107 received CPI before allo-HSCT, and 176 received CPI after allo-HSCT. The most common indication for CPI use was for Hodgkin lymphoma. The CPIs used in various studies included ipilimumab, nivolumab, and pembrolizumab. Among the patients exposed to CPI before allo-HSCT, 56% developed acute GVHD and 29% developed chronic GVHD. Investigators reported 20 deaths, 60% of which were GVHD-related. The overall mortality risk with GVHD is 11%. In this group, investigators noted an objective response rate (ORR) in 68% of patients, with complete remission (CR) in 47%, partial remission (PR) in 21%, and stable disease in 11%. Among the patients who received a CPI after allo-HSCT for disease relapse, 14% developed acute GVHD and 9% developed chronic GVHD. Investigators reported 40 deaths, 28% of which were GVHD-related. The mortality risk with GVHD is approximately 7%. Investigators reported ORR in 54% of patients, with CR in 33%, PR in 21%, and disease stabilization in 5%. After careful evaluation of collective data, we found that CPI use both before and after allo-HSCT can be highly effective, but exposure can lead to a significantly increased risk of GVHD-related morbidity and mortality in this patient population. Despite limited availability of data, there is need for extreme caution while making decisions regarding the use of CPIs. Detailed discussions and prospective well-designed clinical trials are needed to explore this issue further., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Opinion Statement: R-CHOP has been the standard of care for diffuse large B cell lymphoma (DLBCL), curing approximately 60% of patients for more than 2 decades. However, the optimal treatment of patients who are too frail to tolerate this regimen and/or are not candidates for anthracycline therapy continues to be debated. MInT and GELA trials established addition of rituximab to CHOP in DLBCL but excluded patients older than 80 years. Multiple regimens have been tried with varying success in the very elderly, including R-mini-CHOP, R-mini CEOP, R-split CHOP, pre-phase strategies, and R-GCVP. However, there has not been a randomized trial among these strategies. Although addition of novel agents including ibrutinib, brentuximab vedotin, lenalidomide, and many others on the horizon holds promise in this population, none have been tested in a randomized setting or have results awaited. There is also a lack of a validated and easy to use clinical tool in this population to predict patients who will not tolerate R-CHOP. Identifying patients who will not tolerate R-CHOP early with the help of tools like CGA, along with integrating biology-based treatment (ibrutinib, lenalidomide in activated B cell type DLBCL) is being investigated in this population.

Light chain multiple myeloma (LCMM) constitutes approximately 15% of patients with multiple myeloma (MM). It has a poorer prognosis when compared to immunoglobulin (Ig) G or IgA variant. We performed a comprehensive literature search on LCMM and identified a total of 390 articles. After a detailed screening, six studies involving a total of 1054 LCMM patients were included. A literature review revealed bone pain and renal failure as the most common initial sign and symptoms while extramedullary disease (EMD) was acquired later during the progression of the disease. Bortezomib has shown superior efficacy in LCMM patients over nonbortezomib regimens as demonstrated by better overall response rate (95.5% vs. 60%), progression-free survival (PFS) (25% vs. 9% at two years), and overall survival (OS) (24% vs. 9% at five years). Moreover, better PFS was seen, when bortezomib was used in combination with bendamustine compared to dexamethasone (95% vs. 25% at two years). Similarly, better OS (90% at two years) was observed with bortezomib in combination with bendamustine. Monitoring of disease should include serum free light chain levels, as literature review revealed that serum assays were more sensitive in indicating the disease and predicting PFS and OS as compared to urine assays. We provide presentation patterns, clinical rarities, management strategies including their efficacy, and disease monitoring in patients with LCMM in our review paper., Competing Interests: The authors have declared that no competing interests exist.

Hemangiomas of the small intestine are rare and very difficult to diagnose preoperatively. Clinical presentations may include occult or massive gastrointestinal (GI) bleeding, obstruction, intussusception, and perforation. We report a 66-year-old Caucasian male patient with severe anemia secondary to occult GI bleeding from a cavernous hemangioma in the jejunum. A double balloon enteroscopy following capsule endoscopy was performed to obtain biopsy samples, which established the final diagnosis., Competing Interests: The authors have declared that no competing interests exist.