Introduction: Hydroxychloroquine (HCQ) emerged early in the course of the coronavirus disease 2019 (COVID-19) pandemic as a possible drug with potential therapeutic and prophylactic benefits. It was quickly adopted in China, Europe, and the USA. We systematically reviewed the existing clinical evidence of HCQ use for the prevention and treatment of COVID-19.
Methods: We screened for clinical studies describing HCQ administration to treat or prevent COVID-19 in PubMed. We included randomized controlled trials (RCTs), non-randomized comparative cohorts, and case series studies that had all undergone peer review.
Results: A total of 623 studies were screened; 17 studies evaluating HCQ treatment were included. A total of 13 were observational studies, and 4 were RCTs. In terms of effect on mortality rates, observational studies provided conflicting results. As a whole, RCTs, including one large British RCT that has not yet been published, showed no significant effect of HCQ on mortality rates, clinical cure, and virologic response. The use of HCQ as a post-exposure prophylactic agent was found to be ineffective in one RCT.
Conclusion: There is no evidence supporting HCQ for prophylaxis or treatment of COVID-19. Many observational trials were methodologically flawed. Scientific efforts have been disappointingly fragmented, and well-conducted trials have only recently been completed, more than 7 months and 600,000 deaths into the pandemic.
Anatomical dissection is almost ubiquitous in modern medical education, masking a complex history of its practice. Dissection with the express purpose of understanding human anatomy began more than two millennia ago with Herophilus, but was soon after disavowed in the third century BCE. Historical evidence suggests that this position was based on common beliefs that the body must remain whole after death in order to access the afterlife. Anatomical dissection did not resume for almost 1500 years, and in the interim anatomical knowledge was dominated by (often flawed) reports generated through the comparative dissection of animals. When a growing recognition of the utility of anatomical knowledge in clinical medicine ushered human dissection back into vogue, it recommenced in a limited setting almost exclusively allowing for dissection of the bodies of convicted criminals. Ultimately, the ethical problems that this fostered, as well as the increasing demand from medical education for greater volumes of human dissection, shaped new considerations of the body after death. Presently, body bequeathal programs are a popular way in which individuals offer their bodies to medical education after death, suggesting that the once widespread views of dissection as punishment have largely dissipated.
Objective: Early identification of atherosclerosis using a non-invasive tool like ankle–brachial index (ABI) could help reduce the risk for cardiovascular disease among long-term hemodialysis patients. The study objective was to assess the frequency and impact of abnormal ABI as a marker of subclinical peripheral artery disease (PAD) in chronic hemodialysis patients.
Methods: This was a historic cohort study of kidney failure patients on long-term hemodialysis for at least 6 months. The ABI, measured with two oscillometric blood pressure devices simultaneously, was used to assess subclinical atherosclerosis of low limb extremities. Abnormal ABI was defined as ABI <0.9 or >1.3 (PAD present). Survival was defined as time to death. Independent factors associated with abnormal ABI were assessed using multiple logistic regression analysis. Kaplan–Meier method (log-rank test) was used to compare cumulative survival between the two groups; a P value <0.05 was statistically significant.
Results: Abnormal ABI was noted in 50.6% (n=43) of the 85 kidney failure patients included in the study; 42.4% (n=36) had a low ABI, and 8.2% (n=7) had a high ABI. Factors associated with PAD present were cholesterol (adjusted odds ratio [AOR], 1.02; 95% confidence interval [CI], 1.01–1.04; P=0.019), inflammation (AOR, 9.44; 95% CI, 2.30–18.77; P=0.002), phosphocalcic product (AOR, 6.25; 95% CI, 1.19–12.87; P=0.031), and cardiac arrhythmias (AOR, 3.78; 95% CI, 1.55–7.81, P=0.009). Cumulative survival was worse among patients with PAD present (log-rank; P=0.032).
Conclusion: The presence of PAD was a common finding in the present study, and associated with both traditional and emerging cardiovascular risk factors as well as a worse survival rate than patients without PAD.
Query (Q) fever is a zoonotic bacterial infection caused by Coxiella burnetii. In a minority of patients, chronic disease can occur after acute infection. Endocarditis and infections of aneurysms or vascular prostheses are the most common forms of chronic Q fever in adults. We report a case of an elderly female patient with chronic Q fever vertebral osteomyelitis at the site of her previous cement vertebroplasty, complicated by paravertebral abscess. Patient treatment required prolonged drainage in addition to the long duration of antibiotic treatment by doxycycline and hydroxychloroquine. Osteomyelitis is a rare clinical presentation in adults with chronic Q fever. However, it is important to consider Q fever in the differential diagnosis of culture-negative osteomyelitis, especially in countries where C. burnetii is endemic, such as Israel.
Introduction: Endoscopic endonasal transsphenoidal surgery (EETS) on the pituitary gland is considered safe and efficacious. The nasoseptal flap (NSF) is sometimes used to prevent or repair postoperative cerebrospinal fluid (CSF) leaks. Few investigators have quantified long-term quality-of-life (QOL) outcomes regarding sinonasal measures after EETS, with or without involvement of the NSF. This study assesses whether the septal flap affects sinonasal QOL outcomes for patients receiving EETS for pituitary adenoma.
Methods and Materials: This is a retrospective study of patients who underwent EETS between 2013 and 2018. A total of 62 adults completed the Sinonasal Outcome Test-22 (SNOT-22) at least one year after the surgery. Outcome measures were compared between patients who underwent EETS with and without septal flap reconstruction.
Results: For the entire cohort, there were 14 patients (22.6%) who had septal flap reconstruction and 48 patients (77.4%) who did not. Patient demographics, tumor characteristics, surgical outcomes, and duration between surgery and completion of the questionnaire were similar for both groups. The mean SNOT-22 scores in the no reconstruction (NR) group and the nasoseptal flap reconstruction (NSFR) group were similar (P=0.9). In terms of SNOT-22 subdomains (rhinologic symptoms, extranasal rhinologic symptoms, ear/facial symptoms, psychological dysfunction, and sleep dysfunction), no significant differences were found when comparing the groups.
Conclusion: As compared with no reconstructive involvement, NSF utilization does not affect the QOL and nasal symptoms of patients undergoing EETS.
Background: Avoiding rectal thermometry is recommended in patients with neutropenic fever. Permeability of the anal mucosa may result in a higher risk of bacteremia in these patients. Still, this recommendation is based on only a few studies.
Methods: This retrospective study included all individuals admitted to our emergency department during 2014–2017 with afebrile (body temperature <38.3°C) neutropenia (neutrophil count <500 cells/microL) who were over the age of 18. Patients were stratified by the presence or absence of a rectal temperature measurement. The primary outcome was bacteremia during the first five days of index hospitalization; the secondary outcome was in-hospital mortality.
Results: The study included 40 patients with rectal temperature measurements and 407 patients whose temperatures were only measured orally. Among patients with oral temperature measurements, 10.6% had bacteremia, compared to 5.1% among patients who had rectal temperature measurements. Rectal temperature measurement was not associated with bacteremia, neither in non-matched (odds ratio [OR] 0.36, 95% confidence interval [CI] 0.07–1.77) nor in matched cohort analyses (OR 0.37, 95% CI 0.04–3.29). In-hospital mortality was also similar between the groups.
Conclusions: Patients with neutropenia who had their temperature taken using a rectal thermometer did not experience a higher frequency of events of documented bacteremia or increased in-hospital mortality.
Systemic sclerosis (SSc) is a chronic immune-mediated disease characterized by microangiopathy, immune dysregulation, and progressive fibrosis of the skin and internal organs. Though not fully understood, the pathogenesis of SSc is dominated by microvascular injury, endothelial dysregulation, and immune response that are thought to be associated with fibroblast activation and related fibrogenesis. Among the main clinical subsets, diffuse SSc (dSSc) is a progressive form with rapid and disseminated skin thickening accompanied by internal organ fibrosis and dysfunction. Despite recent advances and multiple randomized clinical trials in early dSSc patients, an effective disease-modifying treatment for progressive skin fibrosis is still missing, and there is a crucial need to identify new targets for therapeutic intervention. Eotaxin-2 (CCL24) is a chemokine secreted by immune cells and epithelial cells, which promotes trafficking of immune cells and activation of pro-fibrotic cells through CCR3 receptor binding. Higher levels of CCL24 and CCR3 were found in the skin and sera of patients with SSc compared with healthy controls; elevated levels of CCL24 and CCR3 were associated with fibrosis and predictive of greater lung function deterioration. Growing evidence supports the potency of a CCL24-blocking antibody as an anti-inflammatory and anti-fibrotic modulating agent in multiple preclinical models that involve liver, skin, and lung inflammation and fibrosis. This review highlights the role of CCL24 in orchestrating immune, vascular, and fibrotic pathways, and the potential of CCL24 inhibition as a novel treatment for SSc.
Objectives: This review aimed to critically appraise the evidence for biomarkers in blood serum, gingival crevicular fluid (GCF), saliva, and urine in comparison with standard radiographic indices for skeletal maturation assessment.
Materials and Methods: A thorough literature search in multiple databases was conducted for biomarkers in body fluids for skeletal maturation assessed with cervical vertebrae in lateral cephalograms or on hand-wrist radiographs. Different combinations including free text, MeSH terms, and Boolean operators were used. Two researchers used strict inclusion and exclusion criteria to screen title, abstract, and full text, and used the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 instrument for risk of bias assessment of individual studies. Meta-analysis was performed on eligible studies using RevMan 5 software.
Results: A total of 344 articles were screened, of which 33 met the inclusion criteria and quality assessment. The skeletal maturity indicators included insulin-like growth factors (IGF-1), alkaline phosphatase (ALP), bone-specific alkaline phosphatase (BALP), dehydroepiandrosterone sulfate (DHEAS), vitamin D binding protein (DBP), parathormone-related protein (PTHrP), osteocalcin, metalloproteins, and serotransferrin (TF) along with different metabolites. At puberty, a significant rise was seen in IGF-1, DBP, ALP, osteocalcin, TF, and BALP. However, the serum DHEAS and PTHrP increased from pre-pubertal to post-pubertal stages. Due to the data heterogeneity, a meta-analysis could be performed on seven studies in total on IGF-1 in serum and blood. Of these, five were included for data in males and six in females, and four studies on IGF-1 in serum and blood. A significant difference in IGF-1 levels was seen between stages of peak pubertal growth spurt (CS3 and CS4) and decelerating pubertal growth (CS5) compared with growth initiation stage (CS2).
Conclusions: Pubertal growth spurts were correlated with peak serum IGF-1 and BALP in both sexes individually. Peak ALP levels in GCF were correlated with the pubertal spurt in a combined sample of males and females. Standard biofluid collection protocols and homogeneity in sampling and methodology are strongly recommended for future research.
The appointment of a new chancellor in 1933 marked the beginning of the Third Reich in Germany. The ideology of the Nazi Party focused on establishing a pure Aryan state characterized by nationalism and racial superiority. Their goals would be achieved through a totalitarian form of government that enforced the subjugation, exclusion, and elimination of those they defined as inferior minorities, particularly Jews, who were depicted as non-human. Implementation of the Nazi ideology required the exclusion of Jewish people and other dissenters, particularly Jewish physicians, from their professions. The exclusion of Jewish physicians, referred to herein as a “Medical Professional Elimination Program,” was gradually imposed on other Jewish professions in nations absorbed by the Third Reich, and particularly enforced by incorporated Austria. Why did German and Austrian doctors support the Nazi racial ideology, the removal of Jewish physicians from every possible sphere of influence, and subsequently participate in criminal medical research and experimentation, as well as euthanasia of perceived non-contributors to society, and become involved in refining the effectiveness of the death camps? Was the Medical Professional Elimination Program an opportunistic political concept, or was it part of an entrenched ideology? With these questions in mind, the lives of four key Nazi physicians and two institutions are examined.
Viral hepatitis, primarily caused by hepatitis B virus and hepatitis C virus, is widely recognized for its impact on liver function, but emerging evidence suggests it also affects cognitive function. This review explores the causes, manifestations, and impact of cognitive impairments in patients with viral hepatitis, to better understand this often-overlooked aspect of the disease. A literature review was conducted, focusing on studies published in PubMed up to August 2024. Key areas covered include the pathophysiological mechanisms behind cognitive impairment in viral hepatitis, clinical manifestations observed in affected patients, the implications for their daily functioning and overall well-being, and the tools used in cognitive assessments. Common manifestations included deficits in attention, memory, executive function, and psychomotor speed. These cognitive challenges can significantly impact daily activities, occupational performance, and social interactions, contributing to reduced quality of life. Cognitive impairments in viral hepatitis patients represent a significant concern that extends beyond liver health. Recognizing and addressing these cognitive issues are crucial for improving patient outcomes. Enhanced diagnostic strategies and targeted interventions are needed to better manage cognitive symptoms and support affected individuals in maintaining their quality of life. This narrative review aims to enhance clinical practice and inform future research directions.
