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result(s) for
"Hilal, Talal"
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Current understanding and approach to well differentiated lung neuroendocrine tumors: an update on classification and management
2017
Neuroendocrine tumors (NETs) are rare neoplasms that can arise from any tissue. They are classified based on embryonic gut derivative (i.e. foregut, midgut and hindgut) with midgut tumors being the most common (e.g. gastrointestinal NET). The second most common category of NETs is that which arises from the lung. In fact, 25% of primary lung cancers are NETs, including small cell lung cancer (SCLC), which comprises 20% of all lung cancers. The remaining 5% are large cell neuroendocrine cancer (LCNEC, 3%), typical carcinoids (TCs, 1.8%), and atypical carcinoids (ACs, 0.2%). The less common TCs/ACs are well differentiated lung NETs. Their incidence has been increasing in more recent years and although these tumors are slow growing, advanced disease is associated with poor survival. There have been advances in classification of lung NETs that have allowed for more appropriate management upfront. They are cured by surgical resection when disease is limited. However, advanced and metastatic disease requires medical therapy that is ever changing and expanding. In this review, the aim is to summarize the current understanding and classification of well differentiated lung NETs (i.e. TCs and ACs), and focus on recent updates in medical management of advanced disease, along with a brief discussion on potential future discoveries.
Journal Article
IgG replacement in multiple myeloma
by
Squire, Jacqueline
,
Fonseca, Rafael
,
Freeman, Catherine
in
692/699/249/1570
,
692/699/67/1990/804
,
Agammaglobulinemia - immunology
2024
T cell engagers (TCE) such as chimeric antigen receptor (CAR) T cell therapy and bispecific antibodies (BiAbs) for the treatment of multiple myeloma (MM) have significantly improved clinical outcomes, but have also raised awareness for ensuing post-treatment secondary immunodeficiency and hypogammaglobulinemia (HG). As patients with MM live longer, recurrent infections become a significant component of therapy-associated morbidity and mortality. Treatment of HG with immunoglobulin G replacement therapy (IgG-RT) has been a mainstay of the primary immunodeficiency (PI) world, and extrapolation to MM has recently started to show promising clinical outcomes. However, IgG-RT initiation, dosing, route, timing, monitoring, and management in MM has not been standardized in the setting of TCE. Progress in MM treatment will involve greater recognition and screening of underlying secondary immunodeficiency, identification of risk-stratification markers, optimizing IgG-RT management, and implementing other approaches to decrease the risk of infection. In this review, we summarize infection risk, risk of HG, and management strategies for IgG-RT in patients with relapsed MM after TCE.
Journal Article
Progress in acute myeloid leukaemia: small molecular inhibitors with small benefits
2020
The use of small molecule inhibitors in acute myeloid leukaemia (AML) has become ubiquitous with the US Food and Drug Administration approval of multiple agents between 2017 and 2018. Despite the promise, some of these indications are based on early efficacy data (phase I/II), and single-arm studies, and have not been tested in randomised trials. Furthermore, there are important limitations in the evidence that exists in randomised trials. This perspective aims to summarise the data that formed the basis for approval of gilteritinib, glasdegib, ivosidenib, enasidenib and venetoclax. It also aims to shed a light on some of the limitations in the evidence. Clinicians should exercise caution when using drugs that largely have yet to show an improvement in survival over the standard of care in AML.
Journal Article
Eliminating REMS for CAR T-Cell Therapies: An Opportunity to Improve Access
by
Tsang, Mazie
,
Rosenthal, Allison
,
Orosco-Ttamina, Angel Luis
in
Antigens
,
CD19 antigen
,
Cell therapy
2025
Autologous Chimeric antigen receptor (CAR) T-cell therapies have demonstrated substantial efficacy in patients with relapsed or refractory hematologic malignancies; however, their implementation has been constrained by regulatory barriers. Risk Evaluation and Mitigation Strategies (REMS), mandated by the U.S. Food and Drug Administration (FDA), were initially implemented to mitigate risks associated with cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), and other treatment-related toxicities. On 27 June 2025, the FDA removed REMS requirements for all approved B-cell maturation antigen (BCMA) and CD19-directed autologous CAR T-cell therapies, citing that current product labeling sufficiently communicates safety information. Key regulatory changes include the elimination of site certification and tocilizumab stocking requirements, a reduction in the recommended post-infusion proximity period from four weeks to two weeks, increased flexibility regarding monitoring locations, and a shortened driving restriction from eight weeks to two weeks. This review examines the rationale for the REMS requirements for CAR T-cell therapies, synthesizes contemporary safety data from clinical trials and real-world practice, and explores the implications of this regulatory shift for access to care, particularly in rural and underserved populations. The removal of REMS requirements may facilitate broader implementation of CAR T-cell therapies and alleviate logistical and institutional barriers, offering the potential to expand access while preserving patient safety.
Journal Article
Sudden cardiac arrest in a healthy young athlete
2015
There was no family history of sudden cardiac death or known congenital cardiac conditions. Anomalous origin of the LMCA is a rare entity with a prevalence of 0.2% on autopsy.2 It is a well-recognised cause of sudden cardiac death as described by Cheitlin et al in their review. Once diagnosis is confirmed, treatment is surgical correction with multiple techniques that involve forming a larger ‘neo’ ostium to allow for greater blood flow into the left arterial system.3 Learning points Anomalous origin of the left main coronary artery (LMCA) is a rare but important cause of sudden cardiac death, and should be considered in young patients with unexplained cardiac arrest.
Journal Article
Neutropenic diets to prevent cancer infections: updated systematic review and meta-analysis
by
Jain, Tania
,
Murad, Angela
,
Deleon, Thomas
in
Adult
,
Bacterial Infections - prevention & control
,
Bias
2019
Multiple studies have questioned the benefit of neutropenic diets in decreasing infections in patients with cancer, but recent surveys showed that such diets are still prescribed. In this study, we sought to evaluate the effectiveness of neutropenic diet in decreasing infection and mortality in neutropenic patients with cancer with neutropenia. This review is an update of a previously published systematic review.
We searched different databases to identify comparative studies that investigated the effect of neutropenic diet compared with regular diet in neutropenic adults and children with cancer. We conducted random-effects meta-analyses using the Der-Simonian and Laird method to pool treatment effects from included studies. Outcomes of interest were mortality, bacteremia/fungemia, major infections, quality of life, and the composite outcome for neutropenic fever and/or infection.
We included six studies (five randomised) with 1116 patients, with 772 (69.1%) having underwent haematopoietic cell transplant. There was no statistically significant difference between neutropenic diet and regular diet in the rates of major infections (relative risk [RR] 1.16; 95% CI 0.94 to 1.42) or bacteremia/fungemia (RR 0.96; 95% CI 0.60 to 1.53). In haematopoietic cell transplant patients, neutropenic diet was associated with a slightly higher risk of infections (RR 1.25; 95% CI 1.02 to 1.54). No difference in mortality was seen between neutropenic diet and regular diet (RR 1.08, 95% CI 0.78 to 1.50).
There is currently no evidence to support the use of neutropenic diet or other food restrictions in neutropenic patients with cancer. Patients and clinicians should continue to follow the safe food-handling guidelines as recommended by the U.S. Food and Drug Administration.
Journal Article
Diffuse unresolving pulmonary nodules in a patient with a history of cervical carcinoma
2015
Correspondence to Dr Talal Hilal, talal.hilal@uky.edu Description A 33-year-old woman with a history of cervical carcinoma status post total abdominal hysterectomy and bilateral slapingo-oopherectomy in 2006 presented to the emergency department with acute-onset, sharp, pleuritic chest pain associated with shortness of breath and fever up to 39.9°C. Physical examination revealed a patient in severe respiratory distress with a rate of 54 breaths/min, heart rate of 154 bpm and blood pressure of 104/64 mm Hg. The clinical picture coupled with the presence of diffuse pulmonary nodules was consistent with a diagnosis of septic pulmonary emboli (SPE) from MRSA seeding the IVC clot. To determine definitively the nature of these nodules, a transthoracic biopsy was undertaken, which showed alveolar lung parenchyma with abundant acute and chronic inflammation, and areas of consolidation and necrosis consistent with focal necrotising pneumonia.
Journal Article
Sex Differences in Outcomes of Chimeric Antigen Receptor (CAR) T‐Cell Therapy
2025
ABSTRACT
Background
Chimeric Antigen Receptor (CAR) T‐cell therapy has arisen as a revolutionary treatment for hematologic malignancies. Our study aimed to evaluate how sex differences affect outcomes and complications following CAR T‐cell therapy.
Methods
Utilizing the Nationwide Readmissions Database (2018–2020), we identified patients and divided them into male and female groups. Hospital outcomes and complications were compared among these two groups after propensity score matching to match groups based on comorbidities, producing two comparable cohorts.
Results
We analyzed 2928 patients (1832 males, 62.6%, mean age 60.3 ± 13.7 years; 1096 females, 37.4%, mean age 59.1 ± 13.8 years). After propensity score matching (1:1ratio), 1092 males and females were compared. There were no significant sex differences in early mortality (adjusted odd ratios (aOR): 1.04 [95% CI 0.69–1.57]), 30‐day readmissions (aOR: 1.05 [95% CI 0.86–1.30]), or nonhome discharge (aOR: 0.89 [95% CI 0.60–1.31]). Females had higher odds of leukopenia (aOR: 1.26 [95% CI 1.06–1.50]) but lower odds of acute kidney injury (aOR: 0.68 [95% CI 0.52–0.88]).
Conclusions
No sex differences were found in hospital outcomes, including early mortality, 30‐day readmission, and nonhome discharge after CAR T‐cell therapy.
Journal Article
The frequency of medical reversals in a cross-sectional analysis of high-impact oncology journals, 2009–2018
by
Haslam, Alyson
,
Gill, Jennifer
,
Kim, Myung S.
in
Analysis
,
Biomedical and Life Sciences
,
Biomedicine
2021
Background
Identifying ineffective practices that have been used in oncology is important in reducing wasted resources and harm. We sought to examine the prevalence of practices that are being used but have been shown in RCTs to be ineffective (medical reversals) in published oncology studies.
Methods
We cross-sectionally analyzed studies published in three high-impact oncology medical journals (2009–2018). We abstracted data relating to the frequency and characterization of medical reversals.
Results
Of the 64 oncology reversals, medications (44%) represented the most common intervention type (39% were targeted). Fourteen (22%) were funded by pharmaceutical/industry only and 56% were funded by an organization other than pharmaceutical/industry. The median number of years that the practice had been in use prior to the reversal study was 9 years (range 1–50 years).
Conclusion
Here we show that oncology reversals most often involve the administration of medications, have been practiced for years, and are often identified through studies funded by non-industry organizations.
Journal Article