bluuebunny/crossref_metadata_2025_split huggingface dataset:
Surgical intervention in patients with urothelial carcinoma of the bladder and lymph node metastasis
Authors: Abufaraj Mohammad , Al-Ani Abdallah , AlQudah Alex , Shariat Shahrokh F. 
Published: March 2021

Purpose of review
To systematically review the most recent evidence on the role of surgery in patients with urothelial carcinoma of bladder and lymph node metastasis.

Recent findings
Patients with urothelial carcinoma of bladder and lymph node metastasis have a poor prognosis. The mainstay treatment for these patients is systemic chemotherapy. However, slowly growing body of literature suggests that multimodal therapy comprised of radical cystectomy, lymph node dissection, and perioperative chemotherapy is more effective than either chemotherapy or surgery alone. The timing of chemotherapy, whether preoperative or adjuvant chemotherapy, is still controversial, but the current evidence indicates that patients who achieve a major or complete response after induction chemotherapy appear to benefit from the surgical intervention in the form of radical cystectomy and pelvic lymph node dissection. The limit of lymph node dissection has to be determined.

Summary
Multimodal therapy is associated with better survival outcomes in bladder cancer patients with lymph node metastasis. The current guidelines recommend systemic chemotherapy as the mainstay of treatment for these patients, and there is no convincing evidence on the efficacy of surgical intervention in isolation. Nonetheless, studies comparing multiple treatment modalities demonstrated that surgical salvage therapy is beneficial only when combined with chemotherapy. The methodological limitations of the current literature preclude a robust conclusion of survival advantage. Further studies are needed to help improve imaging for detecting lymph node metastasis and novel strategies to enrich our multimodal therapeutic implementation.
Dual immune check point blockade or immune check point-tyrosine kinase inhibitor combination: as a first-line treatment in metastatic renal cell carcinoma?
Authors: Schmidinger Manuela , Resch Irene , Fajkovic Harun , Remzi Mesut , Shariat Shahrokh F. , Bedke Jens 
Published: March 2021

Purpose of review
To discuss treatment decisions in the first-line setting of metastatic renal cell carcinoma (mRCC).

Recent findings
Immune check point inhibitor (ICI) combinations have replaced sunitinib as the standard of care in the first-line treatment of mRCC. Dual ICI treatment with nivolumab and ipilimumab was shown to significantly improve overall survival and objective response rates. Similarly, the ICI–tyrosine kinase inhibitor combinations pembrolizumab and axitinib and nivolumab and cabozantinib have demonstrated superiority in terms of overall survival, objective response rates and progression-free survival versus sunitinib. The lack of both comparative trials and predictive markers impedes individualized treatment decisions. Clinicians are left to make treatment choices based on clinical and biological factors. These factors may include differences in toxicity profiles, the rate of complete remission, a clinical situation that requires urgent tumor shrinkage, the presence of inflammation, histological or immune-histochemical features and others.

Summary
In the absence of comparative trials, clinical and biological factors may facilitate the choice between various treatment options in the first-line setting of mRCC. In addition, both the experience of the physician with a specific treatment together with patient's preferences and expectations of systemic therapy may be part of the decision-making process.
Salvage management of patients with relapsing testicular germ cell tumors
Authors: Heidenreich Axel , Pfister David , Paffenholz Pia 
Published: March 2021

Purpose of review
This review aims to summarize the latest evidence of medical and surgical treatment options for patients with relapsing testicular germ cell tumors.

Recent findings
Depending on International Germ Cell Cancer Classification Group risk classification 10–50% of patients with metastatic TGCT develop relapse which needs further multimodality treatment. With regard to therapy, early relapses are stratified according to their prognostic risk profile which results in a 3-year overall survival between 6% in the very high to 77% in the very low risk group. Prognostic risk score dictates systemic therapy which might be second line chemotherapy (TIP, PEI) or high dose chemotherapy. Any residual masses following salvage chemotherapy need to be completely resected due the presence of viable cancer and/or teratoma in more than 50% of cases. Targeted therapy in men with druggable mutations is for individualized cases only. Patients with late relapses developing more than 2 years after first-line chemotherapy are best managed by surgery. Desperation surgery is reserved for those patients with rising markers during or immediately after chemotherapy and good risk factors such as rising alpha-fetoprotein, <3 metastatic sites and complete resectability. Multimodality treatment will result in long-term cure of 25% to 60%. Due to the complexity of treatment, chemotherapy as well as surgery should be performed in highly experienced centres only.

Summary
Multimodality treatment to salvage relapsing patients with metastatic testis cancer requires extensive experience for both systemic therapy and surgery. If done properly, it will result in moderate to high cure rates. Personalized therapeutic options are currently evaluated in clinical trials.
Neurotoxicity Biology and Management
Authors: Danish Husain , Santomasso Bianca D. 
Published: March 2021

Abstract
Chimeric antigen receptor (CAR) T-cell therapy is a highly effective new treatment for relapsed and refractory hematological cancers but is associated with the novel treatment-limiting toxicities of cytokine release syndrome and neurotoxicity. Neurotoxicity, now more commonly referred to as immune effector cell–associated neurotoxicity syndrome (ICANS), is a clinical and neuropsychiatric syndrome that can occur in the days to weeks following CAR T-cell and other T-cell–engaging therapies. While the clinical characteristics of ICANS have been well described, its pathophysiology is poorly understood, and best treatment and preventive strategies remain elusive. Clinical trial experience and animal models suggest a central role for endothelial cell dysfunction, myeloid cells, blood–brain barrier disruption, and elevated central nervous system cytokine levels in the development of ICANS. Here we discuss ICANS incidence, clinical features, risk factors, biomarkers, pathophysiology, and grading and management.
Chimeric Antigen Receptor T Cells for B-Cell Lymphoma
Authors: Newcomb Richard , Jacobson Caron 
Published: March 2021

Abstract
Anti-CD19–directed chimeric antigen receptor (CAR) T-cell therapy yields durable remissions in up to 40% of patients with chemoresistant aggressive B-cell non-Hodgkin lymphoma (NHL), a group of patients expected only to survive on average 6 months. Although longer follow-up is needed to define durability, CD19 CAR T cells are demonstrating similar promise in other B-NHL subtypes such as mantle cell lymphoma and the indolent B-cell NHLs. This transformative therapy, however, remains hamstrung by its associated toxicities of cytokine release syndrome and immune effector cell–associated neurotoxicity syndrome, as well as by mechanisms of resistance and relapse and accessibility. To address these limitations, studies are underway to investigate toxicity prevention and mitigation strategies and the development of safer CARs, combination strategies to overcome T-cell exhaustion and dual antigen targeting to combat antigen loss, and alternative cell sources to address cost and manufacturing inefficiencies and resolve issues surrounding T-cell fitness.
Using Adoptive Cellular Therapy for Localized Protein Secretion
Authors: Evans Alysa N. , Lin Heather K. , Hossian A. K. M. Nawshad , Rafiq Sarwish 
Published: March 2021

Abstract
Redirection of T cell cytotoxicity by the chimeric antigen receptor (CAR) structure may not be sufficient for optimal antitumor function in the patient tumor microenvironment. Comodifying CAR T cells to secrete different classes of proteins can be used to optimize CAR T cell function, overcome suppressive signals, and/or alter the tumor microenvironment milieu. These modifications aim to improve initial responses to therapy and enhance the durability of response. Furthermore, CAR T cells can deliver these molecules locally to the tumor microenvironment, avoiding systemic distribution. This approach has been tested in preclinical models using a variety of different classes of agonistic and antagonistic proteins, and clinical trials are currently underway to assess efficacy in patients.
Challenges and Solutions to Bringing Chimeric Antigen Receptor T-Cell Therapy to Myeloid Malignancies
Authors: Borot Florence , Mukherjee Siddhartha , Ali Abdullah Mahmood 
Published: March 2021

Abstract
Myeloid malignancies including myelodysplastic syndromes and acute myeloid leukemia are a group of clonal hematopoietic stem progenitor cell disorders mainly effecting the elderly. Chemotherapeutic approaches improved the outcome in majority of the patients, but it is generally associated with severe toxicities and relapse and does not benefit all the patients. With the success of adoptive cell therapies including chimeric antigen receptor T-cell therapy in treating certain B-cell malignancies, these therapeutic approaches are also being tested for myeloid malignancies, but the preclinical and limited clinical trial data suggest there are significant challenges. The principal hurdle to efficient targeted immunotherapy approaches is the lack of a unique targetable antigen on cancer cells leading to off-target effects including myelosuppression due to depletion of normal myeloid cells. Advanced age of the patients, comorbidities, immunosuppressive bone marrow microenvironment, and cytokine release syndrome are some other challenges that are not unique to myeloid malignancies but pose significant challenge for the successful adaptation of this approach for treatment. In this review, we highlight the challenges and solutions to adopt chimeric antigen receptor T-cell therapies to treat myeloid malignancies.
Improving and Maintaining Responses in Pediatric B–Cell Acute Lymphoblastic Leukemia Chimeric Antigen Receptor–T Cell Therapy
Authors: Arya Rahul , Barrett David M. , Grupp Stephan A. , Melenhorst Jan Joseph 
Published: March 2021

Abstract
Chimeric antigen receptor T therapy has heralded a new era in the treatment of acute lymphoblastic leukemia (ALL) and other hematologic malignancies. In this autologous immunotherapy, patient-derived T cells are genetically engineered and then infused back to kill the leukemia cells. The observed response rates in ALL are a testament to the success of this therapy. However, there have been instances where the patients either did not respond or relapsed after initial response. Emergence of resistance due to antigen loss and T-cell exhaustion has been observed. This poses a challenge in making this therapy successful for every ALL patient and warrants deeper understanding of emergence of resistance and potential approaches to overcome them. Here we discuss current perspectives and advances in this area.
Chimeric Antigen Receptor Design Today and Tomorrow
Authors: Boucher Justin C. , Davila Marco L. 
Published: March 2021

Abstract
The US Food and Drug Administration has approved 3 chimeric antigen receptor (CAR) T-cell therapies. For continued breakthroughs, novel CAR designs are needed. This includes different antigen-binding domains such as antigen-ligand binding partners and variable lymphocyte receptors. Another recent advancement in CAR design is Boolean logic gates that can minimize on-target, off-tumor toxicities. Recent studies on the optimization of costimulatory signaling have also shown how CAR design can impact function. By using specific signaling pathways and transcription factors, CARs can impact T-cell gene expression to enhance function. By using these techniques, the promise of CAR T-cell therapies for solid tumors can be fulfilled.
Is Adoptive Cellular Therapy With Non–T-Cell Immune Effectors the Future?
Authors: Ali Alaa Kassim , Tarannum Mubin , Romee Rizwan 
Published: March 2021

Abstract
Success from checkpoint blockade and adoptive cell therapy has brought a new hope in cancer immunotherapy. Adoptive cell therapy involves the isolation of immune cells, ex vivo activation and/or expansion, and reinfusion into the patients, and their effect can be dramatically increased by the incorporation of chimeric antigen receptors specific to molecules expressed on tumor cells. Chimeric antigen receptor T cells have shown exciting results in the treatment of liquid malignancies; nevertheless, they suffer from limitations including severe adverse effects such as cytokine release syndrome and neurotoxicity seen in patients as well as a potential for causing graft-versus-host disease in an allogeneic setting. It is thus imperial to explore innate immune cells including natural killer cells, macrophages, natural killer T cells, and γδ T cells. Here, we provide a broad overview of the major innate immune cells and their potential for adoptive cell therapy and chimeric antigen receptor engineering.
A Naturalistic Study of Outcomes for Durable Remission in Patients With Bipolar Disorder
Authors: RAPPORT DANIEL , MCGRADY ANGELE , SAJU LINDA , LYNCH DENIS 
Published: March 2021

Objective:
Bipolar disorder is a severe mental illness affecting emotional stability, physical health, and quality of life. In a previous study, we identified medications associated with remission in patients with bipolar disorder. The objective of the current study was to determine the status of the patients after 3 additional years, as well as the medications associated with remission.

Methods:
Data were extracted from clinical records. The criteria for remission in both the original study and the follow-up were 12 continuous months of euthymia, mild symptoms, and no clinical relapse. Active illness was defined as <12 months of remission. Statistical comparisons were made between the remitted and active illness groups on demographics and medication regimens.

Results:
The original study contained 121 patients, 52 of whom were available for follow-up. Of the 121 patients from the original study, 53 (43.8%) were remitted for at least 12 months. Follow-up data were available for 19 of those patients, 15 of whom continued in remission while 4 relapsed. Of the 68 patients who were still ill at the end of the first study, follow-up data were available for 33 patients, 18 of whom had achieved remission at the time of follow-up while 15 continued to be ill. Remitted patients were more likely to be receiving a mood stabilizer (P=0.022) or a combination of a mood stabilizer and an antidepressant (P=0.004).

Conclusions:
On the basis of our results, mood stabilizers and antidepressants were associated with remission in long-term follow-up. Remission may ultimately be possible for many patients who did not succeed initially.
Abrupt Late-onset Psychosis as a Presentation of Coronavirus 2019 Disease (COVID-19): A Longitudinal Case Report
Authors: PARKER CATHERINE , SLAN AARON , SHALEV DANIEL , CRITCHFIELD ADAM 
Published: March 2021

Introduction:
Coronavirus Disease 2019 (COVID-19) is a pandemic infection caused by the Severe Acute Respiratory Syndrome 2 Coronavirus (SARS-2-CoV). Although most prominently associated with pulmonary manifestations, COVID-19 is increasingly implicated in neuropsychiatric complications, including delirium and psychosis. There is a potential causal link between COVID-19 infection and psychotic symptoms; however, case reports to date have been incomplete, as the patients described had known psychiatric histories or other plausible medical causes for altered mental status. We present a longitudinal case of COVID-19 psychosis in a patient who underwent comprehensive diagnostic evaluation. This case is a contribution to the inchoate characterization of neuropsychiatric manifestations of COVID-19 infection.

Case Report:
We present a case of late-onset psychosis in a middle-aged man with no psychiatric history who tested positive for COVID-19 on admission following a recently resolved upper respiratory illness. His acute presentation—characterized by delusions, hallucinations, and disorganized thought and behavior, for which he required inpatient medical admission and subsequent inpatient psychiatric hospitalization—was successfully treated. During his hospitalization, he underwent comprehensive medical and neurological workup (including neuroimaging; electroencephalography; and serum and cerebrospinal fluid testing) that was grossly unremarkable.

Discussion:
Despite myriad potential causes of the patient’s psychosis, this patient’s diagnostic workup was largely unrevealing, apart from his nasopharyngeal SARS-2-CoV reverse transcriptase polymerase chain reaction assay. As such, psychosis secondary to COVID-19 infection emerged as the presumptive diagnosis.
Antimicrobial use in central nervous system infections
Authors: Ciummo Francesco , Srinivas Pavithra , Biedny Jessica 
Published: March 2021

Purpose of review
Central nervous system (CNS) infections are associated with high rates of morbidity and mortality. The purpose of this review is to summarize current antimicrobial therapies, as well as, updates in the management of community-acquired meningitis and healthcare-associated meningitis and ventriculitis.

Recent findings
Due to the increasing rates of multidrug resistant and extensively-drug resistant organisms, available antimicrobials are limited. Novel treatment options include newer systemic antimicrobials and antimicrobials that have previously limited data in the management of CNS infections. Although limited by retrospective data, intrathecal (IT) and intraventricular (IVT) routes of administration offer the opportunity for antimicrobials that conventionally have minimal cerebrospinal fluid (CSF) penetration to achieve high CSF concentrations while minimizing systemic exposure.

Summary
Updates in the use of systemic, IT, and IVT antimicrobials offer promise as therapeutic options for CNS infections. Additional pharmacokinetic and prospective data are needed to confirm these findings.
Application of Local Flaps in Repairing Total and Near-Total Lower Lip Defects of Young Patients
Authors: Bo Qitao , Lu Junxu , Wang Yuanbo , Hu Yanuan , Tang Shoukai , Yang Biaobing 
Published: March 2021

Background:
It has always been a great challenge for clinical doctors to reconstruct total and near-total lower lip defects. Compared with elderly patients, the repair operation in young patients is more difficult where free flaps are usually used for transfer. In order to obtain better postoperative results, the authors combined two kinds of local skin flaps for operation purpose, and evaluated their postoperative clinical effects.

Methods:
From April 2011 to May 2019, a total of 5 young patients with lower lip tumor or trauma were included in this study, with an average age of 30.4 years old. The lesion was all resected and resulted in a defect of 87% to total area of the lower lip, accompanied by a partial defect of the chin each. To repair the defect of the lower lip, the authors firstly used the modified Bernard flap. Then the authors designed the double Abbe flap to perform the operation according to the recovery of the patient 3 months later than the first operation. Finally, the outcomes of either operation were compared upon slit width, mouth opening height, aesthetics, and function of the patients, and statistically analyzed the results.

Results:
All patients underwent the repair of modified Bernard flaps and double Abbe flaps of with no hemodynamic disorder of the flaps and well-recovery. At 3 months after the operation, the average gap width of lip was 4.34 ± 0.24 cm, the average opening height was 3.18 ± 0.28 cm, the average aesthetic score was 7.98 ± 0.51 (full score of 10), and the average functional score was 11.4 ± 0.55 (full score of 12). The 5 patients showed no obvious scar but a good shape on the lower lip. The function of eating, pronunciation, expression of feelings and smiling change were close to normal. Three patients had mild numbness in the lower lip, while the other two had normal sensory function.

Conclusion:
Combined modified Bernard flap and double Abbe flaps can bring out promising reparative outcomes of near-total or total lower lip defects in lower lip in young patients with good aesthetic and functional recovery, which is recommended while considering surgical alternatives.
Osseointegrated Implants for Orbito-Facial Prostheses: Common Complications and Solutions
Authors: Sendul Selam Yekta , Yildiz Aysegul Mavi , Yildiz Ali Atakhan , Akbas Emine 
Published: March 2021

Purpose:
To evaluate anatomical and functional results of osseointegration with magnetic coupling for oculofacial prosthetic rehabilitation after exenteration.

Methods:
This retrospective study included 11 consecutive patients who received orbital reconstruction and oculofacial prosthetic rehabilitation between September 2015 and October 2019. Patient demographics, surgical indications, previous treatment procedures, histopathologic features, and reconstructive procedures were recorded.

Results:
The mean age was 37.81 ± 23 years (range 5–78 years). The mean follow-up was 23.81 ± 12 months (range 10–48 months). The principal diagnoses were squamous cell carcinoma of the eyelids (n = 2/11), mucoepidermoid carcinoma of the maxillary sinus (n = 2/11), rhabdomyosarcoma (n = 1/11), mucormycosis (n = 1/11), neurofibromatosis (n = 1/11), basosquamous carcinoma (n = 1/11), malign melanoma (n = 1/11), primitive neuroectodermal tumor (n = 1/11), and retinoblastoma (n = 1/11). Six of the patients were repaired by primary closure. Procedures performed to reconstruct the orbital cavity included split-thickness skin graft (n = 2/11), temporalis muscle flap (n = 2/11), and frontalis muscle flap (n = 1/11). Nine of the 11 patients who received orbital implants were successfully rehabilitated by epithesis. Postoperative complications included implant loss (n = 4/11), periprosthetic local infection (n = 3/11), and soft tissue overgrowth around the orbital prosthesis (n = 2/11). All patients had Straumann bone level implant (Basel, Switzerland) osseointegrated titanium implants (3.5 mm) placed in a 2-stage procedure over a span of 3 to 4 months with subsequent successful prosthesis fitting.

Conclusion:
The reconstructive methods following orbital exenteration, should be customized according to the patients’ characteristics such as extension of the orbital defect, bone quality, and expectations to achieve satisfactory results.
Reproducible Major Mold for a Silicone Orbital Prosthesis Prototype
Authors: Nguyen Truc Thi Hoang , Eo Mi Young , Cho Yun Ju , Kim Soung Min 
Published: March 2021

Abstract
The implant-supported magnet-retained silicon orbital prosthesis (SOP) was reported as a reliable method to restore the health-related quality of life of patients who underwent facial resection and reconstruction surgery. Currently, fabrication usually requires a long production time and a high level of expertise. Moreover, due to the complex features of facial defects, accurate prosthesis requires many patient fittings.
The prosthesis was designed to repair a complex orbital defect. A reproducible major mold was used to make various silicone prototypes with differences in margin design, silicone shade, and artificial eye's details. The most suitable silicone prototype was chosen for the finalization of the SOP. The patient reported the satisfaction with the function, prosthesis retention, and esthetic restoration.
This clinical study showed that the new technique using a reproducible major mold can allow the fabrication of various prototypes, save time during fitting, and help in improving personalized fabrication of the SOP.