Molnupiravir for the treatment of COVID-19 outpatients: An updated meta-analysis.

BACKGROUND: The majority of available data on molnupiravir come from an unvaccinated COVID-19 population. Therefore, we conducted this meta-analysis to integrate evidence from recent randomized controlled trials (RCTs) as well as observational studies stratified by vaccination status to determine the clinical efficacy and safety of molnupiravir in COVID-19 outpatients. METHODS: We searched PubMed, Embase, the Cochrane Library, medRxiv, and ClinicalTrials.gov from inception to November 2023. We conducted our meta-analysis using RevMan 5.4 with risk ratio (RR) as the effect measure. RESULTS: We included 8 RCTs and 5 observational studies in our meta-analysis. Molnupiravir reduced the risk of all-cause mortality (RR 0.28; 95% CI: 0.20-0.79, I2 = 0%) but did not decrease the hospitalization rate (RR 0.67; 95% CI: 0.45-1.00, I2 = 53%) in the overall population; in the immunized population, no benefits were observed. Molnupiravir lowered the rate of no recovery (RR 0.78; 95% CI: 0.76-0.81, I2 = 0%) and increased virological clearance at day 5 (RR 2.68; 95% CI: 1.94-4.22, I2 = 85%). There was no increase in the incidence of adverse events. CONCLUSIONS: Molnupiravir does not decrease mortality and hospitalization rates in immunized patients with COVID-19. However, it does shorten the disease course and increases the recovery rate. The use of molnupiravir will need to be considered on a case-by-case basis in the context of the prevailing social circumstances, the resource setting, drug costs, and the healthcare burden.

Rare Case of Recurrent Adamantinoma of the Tibia: Limited Efficacy of Pazopanib as a Standalone Treatment.

BACKGROUND Adamantinoma is a rare low-grade malignant bone tumor, usually found in the tibial diaphysis and metaphysis, with histological similarities to mandibular ameloblastoma. The most effective treatment of recurrent adamantinoma is not yet clear. This report is of a 22-year-old woman with recurrent tibial adamantinoma treated with the tyrosine kinase inhibitor pazopanib. CASE REPORT We report the case of a 22-year-old woman who was referred to our center for a suspicious bone lesion in the right tibia. Bone biopsy findings were consistent with an adamantinoma. En bloc resection was completed successfully, with no postoperative complications. Five years later, a positive emission tomography scan revealed mildly increased tracer uptake near the area of the previous lesion and in the right inguinal lymph node. Biopsies of the lesion and inguinal lymph node confirmed recurrence of the adamantinoma. Due to abdominal and pelvic metastasis, the patient underwent surgical debulking, along with an appendectomy, right salpingo-oophorectomy, intraoperative radiation therapy, and hyperthermic intraperitoneal chemotherapy. Subsequently, the patient was placed on pazopanib for 4 months; however, her tumor continued to worsen after 4 months of chemotherapy. Currently, the patient is receiving gemcitabine and docetaxel as second-line medical therapy. CONCLUSIONS This report showed that pazopanib as standalone treatment does not appear to have promising role on patient outcomes. To the best of our knowledge, this is the second report of pazopanib in the treatment of adamantinoma.

Effectiveness of Dermal Regeneration Templates in Managing Acute Full-thickness and Deep Dermal Burn Injuries: A Comparison with Split-thickness Skin Grafts.

Background: The therapeutic challenge of managing acute full-thickness burns is significantly ameliorated with the introduction of dermal regeneration templates (DRTs). However, an updated synthesis of evidence-based data on the efficacy and safety of different DRTs is required. Methods: This systematic review and meta-analysis conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines aims to evaluate the role of various DRTs in comparison with split-thickness skin grafting in managing acute burn injuries after excision and debridement. A total of 28 randomized clinical trials were assessed, encompassing a wide array of DRTs. Results: The study outcomes pointed to the diverse effectiveness of DRTs, with Integra demonstrating peripheral nerve reinnervation potential and TransCyte promoting rapid re-epithelialization. Some DRTs showed scar formation and skin quality comparable to those of autologous skin grafts. In terms of wound infection, certain treatments, including TransCyte, exhibited a significantly low infection rate. The evaluation of scar quality suggested that various interventions produced acceptable or improved outcomes without hypertrophic scarring. Recovery rates after the interventions displayed a range, with certain treatments showing rapid recovery and satisfactory results. Conclusions: The current systematic review points to the potential benefits of DRTs in managing burn wounds. Further research is necessary to shed light on the long-term impacts of these interventions on wound healing, scar quality, and patient recovery.

Innovations in Aortic Valve Replacement: A Comprehensive Overview of the Intuity Rapid Deployment Valve.

Rapid deployment/sutureless (RDS) valves have recently emerged as an innovative surgical solution, providing an alternative to traditional methods of surgical aortic valve replacement (SAVR) by eliminating the need for suture placement and tying. This innovation leads to a reduction in aortic crossclamp and cardiopulmonary bypass times, enhancing the efficiency of the procedure. Among the 2 available RDS valves, the Edwards Intuity valve in particular has been demonstrated to be a particularly promising substitute in the field of SAVR. The Intuity valve distinguishes itself from other RDS and conventional valves by yielding superior outcomes, such as a significant reduction in mortality, increase in the longevity of the valve, and a marked decrease in both mean and peak transvalvular pressure gradients. These benefits collectively contribute to its appeal as a favorable new solution. However, further investigation is needed to conclusively determine the long-term outcomes and safety of RDS valves. Nevertheless, the utilization of the Intuity valve presents an exciting solution to the existing limitations of conventional and minimally invasive SAVR, especially for patients afflicted with severe aortic stenosis.

Prostate cancer among Saudis: a registry review.

Background: Policy makers in Saudi Arabia greatly rely on published studies to make major public health decisions. Prostate cancer (PCa) studies in Saudi Arabia are either outdated or limited to local regions. Aim: The authors aim to analyze the Saudi Cancer Registry to determine the incidence of PCa across all regions of the Kingdom and the risk factors of poor prognosis in the population. Methods: Patients diagnosed with primary PCa from 1 January 2008 to 31 December 2017 were included in the study from the Saudi Cancer Registry. Incidence rates and risk factors for poor survival were calculated. Results: A total of 3607 PCa patients were retrieved. PCa incidence rates ranged from 0.2 to 1.4 per 100 000. Most of the patients were aged 60 and older (86.5%; n=3120), married (97%; n=3497) and lived in the central region (38.1%; n=1375). The mean age at diagnosis was 71.1 (10.8) years. Over half of all tumors were poorly differentiated (64.2%; n=2317), and localized (60.4%; n=2180). The all-time metastasis rate reached 31.4% (n=1131). The lowest mean survival was in those with distant metastasis (P=0.039). Age groups, marital status, tumor morphology, place of residency, and grade were not proven to significantly influence survival. Conclusion: The high metastasis rate and evidence of a greater incidence of newly diagnosed metastatic PCa indicate that the idea of select screening for certain high-risk populations is not farfetched. The authors encourage the promotion of awareness regarding PCa risk factors and screening to optimize prognosis and minimize late presentations and high metastasis rates.

A decade in focus: mixed germ cell tumors with choriocarcinoma components.

Introduction: This 10-year registry review aimed to investigate the clinical behaviour and outcomes of mixed germ cell tumours with choriocarcinoma components, a rare and aggressive subtype of testicular cancer, in Saudi Arabia. The study explores the demographic characteristics of affected patients, tumour profiles, and the mortality rate associated with this malignancy. Methods: Utilizing data from the Saudi Cancer Registry, the authors identified 33 cases of mixed germ cell tumours with choriocarcinoma components among 1001 testicular cancer cases recorded between 2008 and 2017. Demographic information, including age, marital status, region of residency, year of diagnosis, and 10-year survival status, were collected. Tumour factors, such as the basis of diagnosis, origin site, behaviour, grade, extension, and laterality, were also analyzed. Results: The majority of cases (78.8%) occurred in the young age group (18-45 years), and most tumours (97%) originated in normally descended testes. Grade IV (undifferentiated anaplastic) tumours and distant metastasis were present in 45.5% of patients. All cases exhibited malignant tumour behaviour. The overall mortality rate was 15%, with a mean time from diagnosis to death of 7.72 months (range: 0.5-21.5 months). Conclusion: Mixed germ cell tumours with choriocarcinoma components are rare and tend to affect younger populations. These tumours demonstrate aggressive clinical behaviour, with a significant proportion presenting with high-grade lesions and metastasis at diagnosis. The observed mortality rate underscores the poor prognosis associated with this malignancy. Our study provides essential insights into the clinical characteristics of this rare tumour subtype in the Saudi Arabian population, emphasizing the need for further research to identify prognostic factors and optimize management strategies for affected patients.

Neutrophil extracellular traps and long COVID.

Post-acute COVID-19 sequelae, commonly known as long COVID, encompasses a range of systemic symptoms experienced by a significant number of COVID-19 survivors. The underlying pathophysiology of long COVID has become a topic of intense research discussion. While chronic inflammation in long COVID has received considerable attention, the role of neutrophils, which are the most abundant of all immune cells and primary responders to inflammation, has been unfortunately overlooked, perhaps due to their short lifespan. In this review, we discuss the emerging role of neutrophil extracellular traps (NETs) in the persistent inflammatory response observed in long COVID patients. We present early evidence linking the persistence of NETs to pulmonary fibrosis, cardiovascular abnormalities, and neurological dysfunction in long COVID. Several uncertainties require investigation in future studies. These include the mechanisms by which SARS-CoV-2 brings about sustained neutrophil activation phenotypes after infection resolution; whether the heterogeneity of neutrophils seen in acute SARS-CoV-2 infection persists into the chronic phase; whether the presence of autoantibodies in long COVID can induce NETs and protect them from degradation; whether NETs exert differential, organ-specific effects; specifically which NET components contribute to organ-specific pathologies, such as pulmonary fibrosis; and whether senescent cells can drive NET formation through their pro-inflammatory secretome in long COVID. Answering these questions may pave the way for the development of clinically applicable strategies targeting NETs, providing relief for this emerging health crisis.

An unusually high prevalence of isolated prostatic ductal adenocarcinoma among Saudi patients: A registry-based study.

Objective: We conduct a secondary analysis on the demographics, tumor characteristics, survival, and risk factors for mortality among patients with prostatic ductal adenocarcinoma (PDA) in the Kingdom of Saudi Arabia (KSA). Methods: This is a registry-based retrospective study that included all patients diagnosed with prostate cancer in the KSA. The data were collected from the Saudi Cancer Registry, which collects tumor data from all private, military, and health ministry hospitals in Saudi Arabia through five regional offices. Results: Among 3607 prostate cancer patients detected during the specified period, 209 (5.8%) had ductal adenocarcinoma. The median interquartile range age of patients was 72.0 years (64.0-78.0). Adenocarcinoma lesions were malignant among all the patients. Grade III tumors were most frequently apparent lesions (61.2%), followed by Grade II tumors (26.3%), Grade I tumors (7.2%), and Grade VI tumors (5.3%). A total of 33 patients died, representing 15.8% of the whole sample. The 1-year survival rate was 78.1%. More than a third of patients who were residing in the Western region deceased (38.0%), whereas no deaths were reported in other regions with a statistically significant difference based on regions (P < 0.001). Conclusion: To the best of our knowledge, this is the first registry-based study to investigate PDA in the KSA; these efforts were done to further understand this deadly condition and to further enhance patient care in the KSA.

Cerebrospinal fluid microRNAs as potential biomarkers in Alzheimer's disease.

Alzheimer's disease (AD) is the leading form of dementia worldwide, but its early detection and diagnosis remain a challenge. MicroRNAs (miRNAs) are a group of small endogenous RNA molecules that regulate mRNA expression. Recent evidence suggests miRNAs play an important role in the five major hallmarks of AD pathophysiology: amyloidogenesis, tauopathy, neuroinflammation, synaptic dysfunction, and neuronal death. Compared to traditional biomarkers of AD, miRNAs display a greater degree of stability in cerebrospinal fluid. Moreover, aberrant changes in miRNA expression can be measured over time to monitor and guide patient treatment. Specific miRNA profiles and combinations may also be used to distinguish AD subjects from normal controls and other causes of dementia. Because of these properties, miRNAs are now being considered as promising and potential biomarkers of AD. This review comprehensively summarizes the diagnostic potential and regulatory roles miRNAs play in AD.

Giant staghorn stone causing inferior vena cava compression: a novel case report.

Staghorn calculi (SC) are defined as large kidney stones that fill the renal pelvis and at least one renal calyx. They represent 10-20% of all renal stones in developing countries and require prompt diagnosis and management. Massive SC (over 5 cm) are treated exclusively via open surgery, despite percutaneous nephrolithotomy (PCNL) being the gold standard treatment for large stones. Descriptions of PCNL for massive SC are very limited in the literature. Case Presentation: We report a case of a 63-year-old male who presented with chronic abdominal pain, hepatosplenomegaly, and normal renal function. He was later diagnosed with polycythemia vera. Computed tomography of the abdomen revealed massive, bilateral staghorn stones measuring 7.3×5.5 cm and 1.8×4.5 cm on the right and left, respectively. Additionally, the right stone was found to be compressing the inferior vena cava (IVC). The patient was promptly scheduled for right-sided PCNL and the target of 80% stone fragmentation was successfully attained. Discussion: We present the first case of a stone of such size in the Middle East, as well as the first known case of a renal stone compressing the IVC. Unlike previous reports, the stone was successfully fragmented via PCNL - a procedure that has not been described for stones of such size. Conclusion: This report highlights that ultrasound-guided PNCL without any other intervention is sufficient for the successful treatment of giant SC. Greater research is needed on the potential utility of using ultrasound-guided PCNL for the fragmentation of stones sized over 5 cm.

Utilization of the emergency department by kidney transplant recipients: a retrospective cohort study from a high-volume transplant center.

This study aims to assess the trends of emergency department (ED) visits among kidney transplant recipients in a high-volume transplant centre. Methods: This retrospective cohort study targeted patients who underwent renal transplantation at a high-volume transplant centre from 2016 to 2020. The main outcomes of the study were ED visits within 30 days, 31-90 days, 91-180 days, and 181-365 days of transplantation. Results: This study included 348 patients. The median (interquartile range) age of patients was 45.0 years (30.8, 58.2). Over half of the patients were male (57.2%). There was a total of 743 ED visits during the first year after discharge. 19% (n=66) were considered high-frequency users. High-volume ED users tended to be admitted more frequently as compared to those with low frequencies of ED visits (65.2% vs. 31.2%, respectively, P<0.001). Conclusion: As evident by the large number of ED visits, suitable coordination of management through the ED remains a pivotal component of post-transplant care. Strategies addressing prevention of complications of surgical procedures or medical care and infection control are aspects with potential for enhancement.

Neutrophil extracellular traps in central nervous system pathologies: A mini review.

Neutrophils are the first cells to be recruited to sites of acute inflammation and contribute to host defense through phagocytosis, degranulation and neutrophil extracellular traps (NETs). Neutrophils are rarely found in the brain because of the highly selective blood-brain barrier (BBB). However, several diseases disrupt the BBB and cause neuroinflammation. In this regard, neutrophils and NETs have been visualized in the brain after various insults, including traumatic (traumatic brain injury and spinal cord injury), infectious (bacterial meningitis), vascular (ischemic stroke), autoimmune (systemic lupus erythematosus), neurodegenerative (multiple sclerosis and Alzheimer's disease), and neoplastic (glioma) causes. Significantly, preventing neutrophil trafficking into the central nervous system or NET production in these diseases alleviates brain pathology and improves neurocognitive outcomes. This review summarizes the major studies on the contribution of NETs to central nervous system (CNS) disorders.

Moyamoya syndrome secondary to mitochondrial disease in a patient with partial trisomy 13q14 and 13q31: A novel case report and literature review.

Moyamoya syndrome (MMS) is a cerebrovascular disease characterized by stenosis of the internal carotid arteries and the formation of an abnormal vascular network at the base of the brain. MMS usually occurs secondary to various conditions, particularly Down syndrome, and sickle cell anemia, and presents with motor deficits, sensory symptoms, recurrent ischemic strokes, hemodynamic transient ischemic attacks, recurrent seizures, and hemorrhage. Trisomy 13 (Patau Syndrome) is a chromosomal abnormality that may be characterized by full or partial trisomy of chromosome 13. Phenotypic features of partial trisomy 13 include leukoencephalopathy, hippocampal hypoplasia, intellectual disability, facial anomalies, and others. Herein, we report a case of a 19-year-old female diagnosed with partial trisomy 13q, characterized by two large duplications in the 13q14 and 13q31 regions, with trisomy-induced bilateral MMS - the first known case to be discussed in literature. Particularly, our patient was identified to have a gain of 22Mb within the 13q14.11q21.31 region - a duplication that has not been described previously. Our patient suffered four strokes between the ages of 5 and 7, later developing intractable seizures, hemiplegia, spasticity in all limbs, global delay, and regression. Despite bilateral encephaloduroarteriosynangiosis and being on several antiepileptic medications, the MMS continued to progress, confounded by the partial trisomy 13. Studies must elucidate the association between mitochondrial damage and MMS, as well as mechanisms of epilepsy associated with chromosomal abnormalities, particularly in the context of underlying mitochondrial diseases.

Recurrence of methotrexate-induced leukoencephalopathy after methotrexate rechallenge: A case report and literature review.

Methotrexate (MTX) is potent chemotherapeutic agent, often administered intrathecally to treat or prevent central nervous system involvement in lymphomas and leukemias, particularly T-cell lymphoblastic leukemia (T-LBL). MTX has been linked to adverse neurologic effects that mimic acute stroke, including facial drooping, hemiplegia, impaired consciousness, and seizures, as well as changes on imaging-known as MTX-induced leukoencephalopathy (LE). We report a case of a 17-year-old male diagnosed with T-LBL, who had been receiving MTX chemotherapy for 4 months. After receiving his fourth dose of MTX, he presented to the emergency department with fever, facial drooping, and acute left-sided weakness. Brain magnetic resonance imaging (MRI) revealed bilateral deep white matter T2 hyperintense foci, increased on the right, with associated diffusion restriction in the right centrum semiovale-consistent with MTX-induced LE. After his symptoms resolved, he was discharged on leucovorin. Six months afterward, he was rechallenged with MTX and developed recurrence of symptoms. Repeat MRI showed well-defined T2/FLAIR hyperintensities in the right centrum semiovale without corresponding diffusion restriction. The left centrum semiovale hyperintensity became less conspicuous in comparison to the previous MRI study. We report a rare case of recurrence of LE after MTX rechallenge and discuss mechanisms, best imaging modalities, and possible treatment options for MTX-induced LE. Given the ominous presentation of MTX-induced LE, we urge clinicians to maintain a high index of suspicion for this condition. Further research is necessary to understand why only certain patients develop recurrence of LE after subsequent doses of MTX.

A retrospective cohort study on the use of machine learning to predict stone-free status following percutaneous nephrolithotomy: An experience from Saudi Arabia.

Background: Machine learning techniques have been used extensively in the field of clinical medicine, especially when used for the construction of prediction models. The aim of the study was to use machine learning to predict the stone-free status after percutaneous nephrolithotomy (PCNL). Materials and methods: This is a retrospective cohort study of 137 patients. Data from adult patients who underwent PCNL at our institute were used for the purpose of this study. Three supervised machine learning algorithms were employed: Logistic Regression, XGBoost Regressor, and Random Forests. A set of variables comprising independent attributes including age, gender, body mass index (BMI), chronic kidney disease (CKD), hypertension (HTN), diabetes mellitus, gout, renal and stone factors (previous surgery, stone location, size, and staghorn status), and pre-operative surgical factors (infections, stent, hemoglobin, creatinine, and bacteriuria) were entered. Results: 137 patients were identified. The majority were males (65.4%; n = 89), aged 50 years and above (41.9%; n = 57). The stone-free status (SFS) rate was 86% (n = 118). An inverse relation was detected between SFS, and CKD and HTN. The accuracies were 71.4%, 74.5% and 75% using Logistic Regression, XGBoost, and Random Forest algorithms, respectively. Stone size, pre-operative hemoglobin, pre-operative creatinine, and stone type were the most important factors in predicting the SFS following PCNL. Conclusion: The Random Forest model showed the highest efficacy in predicting SFS. We developed an effective machine learning model to assist physicians and other healthcare professionals in selecting patients with renal stones who are most likely to have successful PCNL treatment based on their demographics and stone characteristics. Larger multicenter studies are needed to develop more powerful algorithms, such as deep learning and other AI subsets.

Primary omental pregnancy in a subseptate uterus: A novel case report and literature review.

Introduction and importance: Ectopic pregnancy is defined as a pregnancy in which the fertilized ovum implants itself in a location other than the uterine endometrium. Abdominal ectopic pregnancies involve the implantation and development of the embryo within the peritoneal cavity. Primary omental pregnancies are the rarest form of abdominal pregnancy and possibly the rarest extrauterine gestation. Case presentation: We report the first case of a primary omental pregnancy in a subseptate uterus in literature. Our patient, a 33-year-old female, G8P4+3, presented with nausea, severe abdominal pain, and vaginal spotting at 6 weeks' gestational age. She had mild tenderness below the umbilicus, with positive cervical and right adnexal tenderness. 2D-ultrasound revealed a subseptate uterus, normal ovaries and fallopian tubes, absence of a gestational sac, and a 4x3x2.5 cm mass in the right adnexa. A mini-laparotomy was performed due to suspicion of ruptured tubal pregnancy, revealing a primary omental pregnancy which was managed via partial omentectomy. Clinical discussion: Ectopic pregnancies have ambiguous presentations, however correct diagnosis and management is crucial to prevent complications. A high index of suspicion must be exercised to make an accurate diagnosis of primary omental pregnancy. A subseptate uterus is a subtype of the most common uterine anomaly and should be investigated via 3D-ultrasound and magnetic resonance imaging as it causes increased risk of primary omental implantation. Conclusion: Correct identification of subseptate or septate uteri is vital. Greater research is needed to elucidate the association between septate or subseptate uteri and ectopic pregnancy, particularly primary omental pregnancy.

Emerging role of neutrophil extracellular traps in the complications of diabetes mellitus.

Immune dysfunction is widely regarded as one of the central tenants underpinning the pathophysiology of diabetes mellitus (DM) and its complications. When discussing immunity, the role of neutrophils must be accounted for: neutrophils are the most abundant of the circulating immune cells and are the first to be recruited to sites of inflammation, where they contribute to host defense via phagocytosis, degranulation, and extrusion of neutrophil extracellular traps (NETs). NETs are composed of DNA associated with nuclear and cytosolic neutrophil proteins. Although originally reported as an antimicrobial strategy to prevent microbial dissemination, a growing body of evidence has implicated NETs in the pathophysiology of various autoimmune and metabolic disorders. In these disorders, NETs propagate a pathologic inflammatory response with consequent tissue injury and thrombosis. Many diabetic complications-such as stroke, retinopathy, impaired wound healing, and coronary artery disease-involve these mechanisms. Therefore, in this review, we discuss laboratory and clinical data informing our understanding of the role of NETs in the development of these complications. NET markers, including myeloperoxidase, citrullinated histone H3, neutrophil elastase, and cell-free double-stranded DNA, can easily be measured in serum or be detected via immunohistochemical/immunocytochemical staining of tissue specimens. Therefore, NET constituents potentially constitute reliable biomarkers for use in the management of diabetic patients. However, no NET-targeting drug is currently approved for the treatment of diabetic complications; a candidate drug will require the outcomes of well-designed, robust clinical trials assessing whether NET inhibition can benefit patients in terms of morbidity, quality of life, health expenditures, and mortality. Therefore, much work remains to be done in translating these encouraging pieces of data into clinical trials for NET-targeting medications to be used in the clinic.

Heart failure in systemic right ventricle: Mechanisms and therapeutic options.

d-loop transposition of the great arteries (d-TGA) and congenitally corrected transposition of the great arteries (cc-TGA) feature a right ventricle attempting to sustain the systemic circulation. A systemic right ventricle (sRV) cannot support cardiac output in the long run, eventually decompensating and causing heart failure. The burden of d-TGA patients with previous atrial switch repair and cc-TGA patients with heart failure will only increase in the coming years due to the aging adult congenital heart disease population and improvements in the management of advanced heart failure. Clinical data still lags behind in developing evidence-based guidelines for risk stratification and management of sRV patients, and clinical trials for heart failure in these patients are underrepresented. Recent studies have provided foundational data for the commencement of robust clinical trials in d-TGA and cc-TGA patients. Further insights into the multifactorial nature of sRV failure can only be provided by the results of such studies. This review discusses the mechanisms of heart failure in sRV patients with biventricular circulation and how these mediators may be targeted clinically to alleviate sRV failure.