Choosing and accessing COVID-19 treatment options: a qualitative study with patients, caregivers, and health care providers in Lebanon.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has strained healthcare systems globally, particularly in terms of access to medicines. Lebanon has been greatly affected by the pandemic, having faced concomitant financial and economic crises. The objective of the study was to understand the experiences of patients with COVID-19 in Lebanon, as well as those of their families, and healthcare providers, with regards to their treatment decisions and accessibility to COVID-19 medicines. METHODS: For this qualitative study, we conducted 28 semi-structured interviews. We used purposive sampling to recruit participants with a diverse range of perspectives. The data collection phase spanned from August to November 2021 and was conducted virtually. After transcribing and translating the interviews, we employed thematic analysis to identify recurring themes and patterns. RESULTS: In total, 28 individuals participated in this study. Participants highlighted challenges owing to the COVID-19 pandemic and economic crisis. Accessing COVID-19 medicines posed major hurdles for physicians and patients, given limited availability, global shortages, local circumstances, community hoarding and stockpiling by pharmacies. Providers based treatment decisions on research, local and international practice guidelines, experiences and expert feedback. Patients sought information from social media, community members and physicians, as well as through word of mouth. Accessing medicines involved navigating the healthcare system, the black market, charities, personal networks and political parties and sourcing from abroad. The medicines were either free, subsidized or at inflated costs. CONCLUSIONS: This study highlights the diversity and complexity of factors influencing decision-making and accessing medicines during the COVID-19 pandemic in Lebanon. Future research should explore strategies for ensuring medicine access during crises, drawing insights from comparative studies across different countries.

Hepatocyte nuclear factor 4α mediated quinolinate phosphoribosylltransferase (QPRT) expression in the kidney facilitates resilience against acute kidney injury.

Nicotinamide adenine dinucleotide (NAD+) levels decline in experimental models of acute kidney injury (AKI). Attenuated enzymatic conversion of tryptophan to NAD+ in tubular epithelium may contribute to adverse cellular and physiological outcomes. Mechanisms underlying defense of tryptophan-dependent NAD+ production are incompletely understood. Here we show that regulation of a bottleneck enzyme in this pathway, quinolinate phosphoribosyltransferase (QPRT) may contribute to kidney resilience. Expression of QPRT declined in two unrelated models of AKI. Haploinsufficient mice developed worse outcomes compared to littermate controls whereas novel, conditional gain-of-function mice were protected from injury. Applying these findings, we then identified hepatocyte nuclear factor 4 alpha (HNF4α) as a candidate transcription factor regulating QPRT expression downstream of the mitochondrial biogenesis regulator and NAD+ biosynthesis inducer PPARgamma coactivator-1-alpha (PGC1α). This was verified by chromatin immunoprecipitation. A PGC1α - HNF4α -QPRT axis controlled NAD+ levels across cellular compartments and modulated cellular ATP. These results propose that tryptophan-dependent NAD+ biosynthesis via QPRT and induced by HNF4α may be a critical determinant of kidney resilience to noxious stressors.

Validation of the new ABC score for predicting 30-day mortality in gastrointestinal bleeding.

BACKGROUND/AIM: The ABC score is a new pre-endoscopic scoring system that was recently developed to accurately predict one-month mortality in upper and lower gastrointestinal bleeding (GIB). We aim to validate this new score on a cohort of Lebanese patients treated in a tertiary care center and to compare it to currently existing scores. METHODS: Adult patients admitted to the American University of Beirut Medical Center (AUBMC) with overt GIB between January 2013 and August 2020 were included. The area under receiver operating characteristic (AUROC) curves of the ABC score in predicting 30-day mortality was calculated using the SPSS software. Other optimal existing scores for predicting mortality (the Oakland score for lower GIB, the AIMS-65 and the Rockall scores for upper GIB)s were also assessed and compared to the ABC score. RESULTS: A total of 310 patients were included in our study. For upper GIB, the ABC score showed good performance in predicting 30-day mortality (AUROC: 0.79), outperforming both the AIMS-65 score (AUROC 0.67, p < 0.001) and the Rockall score (AUROC: 0.62, p < 0.001). For lower GIB, the ABC score also had good performance which was comparable to the Oakland score (AUROC: 0.70 vs 0.56, p = 0.26). CONCLUSION: In our cohort of patients, the ABC score demonstrated good performance in predicting 30-day mortality for patients with upper and lower GIB compared to other established risk scores, which may help guide management decisions. This simple and novel score provides valuable prognostic information for patients presenting with GIB and appears to be reproducible in different patient populations.

Imaging of Adult Malignant Soft Tissue Tumors of the Spinal Canal: A Guide for Spine Surgeons.

BACKGROUND: Malignant soft tissue spinal canal tumors compromise 20% of all spinal neoplasms. They may be primary or metastatic lesions, originating from a diverse range of tissues within and surrounding the spinal canal. These masses can present as diverse emergencies such as secondary cauda equina syndrome, vascular compromise, or syringomyelia. Interpretation of malignant soft tissue spinal canal tumors imaging is an essential for non-radiologists in the setting of emergencies. This task is intricate due to a great radiologic pattern overlap among entities. METHODS: We present a step-by-step strategy that can guide nonradiologists identify a likely malignant soft tissue lesion in the spinal canal based on imaging features, as well as a review of the radiologic features of malignant soft tissue spinal canal tumors. RESULTS: Diagnosis of soft tissue spinal canal malignancies starts with the identification of the lesion's spinal level and its relationship to the dura and medulla. The second step consists of characterizing it as likely-malignant based on radiological signs like a larger size, ill-defined margins, central necrosis, and/or increased vascularity. The third step is to identify additional imaging features such as intratumoral hemorrhage or cyst formation that can suggest specific malignancies. The physician can then formulate a differential diagnosis. The most encountered malignant soft tissue tumors of the spinal canal are anaplastic ependymomas, anaplastic astrocytomas, metastatic tumors, lymphoma, peripheral nerve sheath tumors, and central nervous system melanomas. A review of the imaging features of every type/subtype of lesion is presented in this work. Although magnetic resonance imaging remains the modality of choice for spinal tumor assessment, other techniques such as dynamic contrast agent-enhanced perfusion magnetic resonance imaging or diffusion-weighted imaging could guide diagnosis in specific situations. CONCLUSIONS: In this review, diagnostic strategies for several spinal cord tumors were presented, including anaplastic ependymoma, metastatic spinal cord tumors, anaplastic and malignant astrocytoma, lymphoma, malignant peripheral nerve sheath tumors , and primary central nervous system melanoma. Although the characterization of spinal cord tumors can be challenging, comprehensive knowledge of imaging features can help overcome these challenges and ensure optimal management of spinal canal lesions.

The Significance of NAD+ Biosynthesis Alterations in Acute Kidney Injury.

Acute kidney injury (AKI) is a serious and highly prevalent disease, yet only supportive treatment is available. Nicotinamide adenine dinucleotide (NAD+) is a cofactor necessary for adenosine triphosphate (ATP) production and cell survival. Changes in renal NAD+ biosynthesis and energy utilization are features of AKI. Targeting NAD+ as an AKI therapy shows promising potential. However, the pursuit of NAD+-based treatments requires deeper understanding of the unique drivers and effects of the NAD+ biosynthesis derangements that arise in AKI. This article summarizes the NAD+ biosynthesis alterations in the kidney in AKI, chronic disease, and aging. To enhance this understanding, we explore instances of NAD+ biosynthesis alterations outside the kidney in inflammation, pregnancy, and cancer. In doing so, we seek to highlight that the different NAD+ biosynthesis pathways are not interconvertible and propose that the way in which NAD+ is synthesized may be just as important as the NAD+ produced.

States of quinolinic acid excess in urine: A systematic review of human studies.

Introduction: Quinolinic acid is an intermediate compound derived from the metabolism of dietary tryptophan. Its accumulation has been reported in patients suffering a broad spectrum of diseases and conditions. In this manuscript, we present the results of a systematic review of research studies assessing urinary quinolinic acid in health and disease. Methods: We performed a literature review using PubMed, Cochrane, and Scopus databases of all studies reporting data on urinary quinolinic acid in human subjects from December 1949 to January 2022. Results: Fifty-seven articles met the inclusion criteria. In most of the reported studies, compared to the control group, quinolinic acid was shown to be at increased concentration in urine of patients suffering from different diseases and conditions. This metabolite was also demonstrated to correlate with the severity of certain diseases including juvenile idiopathic inflammatory myopathies, graft vs. host disease, autism spectrum disorder, and prostate cancer. In critically ill patients, elevated quinolinic acid in urine predicted a spectrum of adverse outcomes including hospital mortality. Conclusion: Quinolinic acid has been implicated in the pathophysiology of multiple conditions. Its urinary accumulation appears to be a feature of acute physiological stress and several chronic diseases. The exact significance of these findings is still under investigation, and further studies are needed to reveal the subsequent implications of this accumulation.

The burden of Hepatitis E virus in the Middle East and North Africa region: a systematic review.

INTRODUCTION: Hepatitis E virus is a leading cause of hepatitis in the Middle East and North Africa region. Although several countries in this area were shown to be endemic for hepatitis E, little is known about the epidemiology and possible preventive measures. In this manuscript, we present the results of a systematic review addressing the seroprevalence of hepatitis E antibodies in the Middle East and North Africa region. Subsequently, we discuss the main prevention strategies for this virus. METHODOLOGY: We performed a literature review using the PubMed Database of all the Studies reporting data on hepatitis E seroprevalence (Anti-hepatitis E IgM and IgG) among the 20 countries of the Middle East and North Africa region from January 2000 to July 2021. RESULTS: Eighty-nine articles were identified and included in our review. Ten of the MENA countries did not have any study that fits our criteria. Egypt and Iran were the countries with the highest IgG seroprevalence for hepatitis E reaching 85.1% and 68.6% respectively. Concerning acute hepatitis E presentations, Iraq and Egypt were shown to have the highest IgM seroprevalence reaching 38.1% and 35.3% respectively. Hemodialysis and poly-transfused patients as well as patients with concomitant hepatotropic viruses' infections were reported to have a higher seroprevalence than the general population. CONCLUSIONS: Hepatitis E is a major healthcare problem in the endemic Middle East and North Africa region. Even though no definite prevention strategy was described until today, implementing multiple minor precautionary approaches could help reduce the virus spread.

Post-traumatic stress symptoms experienced by healthcare workers in Lebanon four months following Beirut's ammonium nitrate explosion: a survey-based study.

BACKGROUND: On August 4, 2020, Lebanon faced one of the deadliest mass casualty explosions the world has witnessed during the twenty-first century. The human and emotional tolls were heavy on attending physicians, clinical fellows, residents, interns, medical students, and registered nurses, who were working in dramatic conditions, triaging, and treating thousands of blast-related casualties. We evaluated the risk of developing post-traumatic stress disorder symptoms (PTSS), among these healthcare workers (HCWs) from different Lebanese hospitals. METHODS: This is a multicentered, cross-sectional study that was conducted in December 2020, using an online questionnaire that evaluated the risk of developing PTSS based on the validated self-reported PTSD-Checklist for DSM-V (PCL-5). We also explored possible correlates with the participants' socio-demographic characteristics, job profile, mental health, and blast-related events. RESULTS: Out of 519 participants, 44% were at high risk of developing PTSS following Beirut-blast. Nurses, attending physicians, fellows, and participants who are older in age, married, or working at specific hospitals, were at a higher risk. Those identified at higher risk of PTSS were surgeons, anesthesiologists, emergency medicine doctors, or radiologists; and they were more likely to be willing to migrate; having a prior history of psychiatric medication intake for PTSD treatment, a prior history of PTSD, or a personal history of seeking mental health service. At last, the latter two parameters as well as the number of examined injuries, severe home damage, and testing positive for the COVID-19 virus during the two weeks' period that followed the blast were found to be predictors for the development of PTSS. CONCLUSION: Lebanese in-hospital HCWs were found to be at a high risk of developing PTSS following the Beirut-Blast, thus we recommend public health authorities to provide adequate resources to avoid the emergence of mental illnesses among these rescuers.

The role of funduscopy in severe thrombocytopenia: A prospective study.

PURPOSE: Platelet transfusions for patients suffering from severe thrombocytopenia are regulated by clinical bleedings and platelet counts. The aim of this study was to assess the prevalence of retinal hemorrhage in patients with hematologic and oncologic malignancies and severe thrombocytopenia, and to determine the benefit of systematic funduscopic examination in this setting. MATERIALS AND METHODS: Hospitalized patients with hematologic and oncologic malignancies having a platelet count less than 25,000 per µL underwent indirect ophthalmoscopy. The prevalence of retinal hemorrhage and its correlation with different patients' characteristics were determined. The decision to transfuse platelets or not following bedside indirect ophthalmoscopy was left at the discretion of the treating physician. RESULTS: A total of 34 severe thrombocytopenic patients were included in the study. The prevalence of retinal hemorrhage was detected in 10 patients (29.4%). No significant correlation was found between the occurrence of retinal hemorrhage and age, platelet count or thrombocytopenia etiology (P>0.05). No significant difference was found concerning the rate of transfusion between those with and without retinal hemorrhage. CONCLUSION: According to our statistical results, retinal hemorrhage is a frequent finding in severely thrombocytopenic patients. Early detection may lead to an increase in the platelet transfusion threshold from to 30,000 per µL offering additional protection against spontaneous bleedings. Funduscopy is a safe and easy exam to perform systematically in patients with severe thrombocytopenia.

Significance of granulomas in the outcomes of Crohn's disease patients.

Background: The presence of granulomas in the gastrointestinal (GI) tract is one of the characteristic histologic features of Crohn's disease (CD). The clinical significance of granulomas remains unclear. In this study, we aimed to determine whether the presence of granulomas on endoscopic pinch biopsy or surgical resection from the upper or lower GI tract is associated with worse outcomes among patients with CD. Methods: This was a retrospective chart review of patients with CD evaluated at a tertiary care center between 1996 and 2019. Patients were divided into 2 groups based on the presence or absence of granulomas on GI histology. Clinical and laboratory data, and outcomes of interest, were obtained from the electronic medical records. Patients' characteristics and outcomes were compared between the 2 groups. Results: A total of 237 patients were included in our study; 41 (17.3%) had granulomas on their biopsy/resection specimen. The presence of granulomas in the GI tract was significantly associated with the development of intra-abdominal abscesses and/or fistulas (P=0.037), greater utilization of immunomodulators (P=0.029), and greater use of immunosuppressive medications (immunomodulator and/or biologic therapy) (P=0.015). No significant differences were found between the 2 groups in terms of number of hospitalizations, presence of perianal disease, intestinal resection, mean age, mean age at initial diagnosis of CD, duration of disease, sex, or smoking history. Conclusions: The presence of granulomas in the GI tract of CD patients may serve as a prognostic biomarker of worse disease severity. Larger studies are needed to better validate this finding.

PARP inhibitors: a tsunami of indications in different malignancies.

The evolution of precision medicine in the field of oncology has led to a radical change in the course of malignancies. PARP inhibitors are drugs that block the activity of the PARP enzyme responsible for base excision repair and have shown significant positive response when used for tumors lacking homologous recombination, namely high efficacy among BRCA-mutated tumors. Since 2014, when olaparib received an accelerated US FDA approval in ovarian cancer, we witnessed many other FDA approvals for olaparib, rucaparib, niraparib and talazoparib. Additionally, many Phase I, II and III trials were published presenting revolutionizing results. Other ongoing trials combined PARP inhibitors with checkpoint inhibitors. We aimed in this review to state the FDA approvals for PARP inhibitors in breast, ovarian, fallopian tube and primary peritoneal cancers, report the major published trials in high impact medical journals, and mention the ongoing trials combining these drugs with checkpoint inhibitors.