Multifaceted realities of scrub typhus: a case series from southern India.

Scrub typhus is an acute febrile illness caused by Orientia tsutsugamushi, a Gram-negative bacillus, commonly occurring in the Asia-Pacific region. It is transmitted to humans by the bite of an infected Leptotrombidium mite and the bacterium causes endothelial dysfunction resulting in widespread vasculitis and the possible development of thrombocytopenia, meningitis, acute respiratory distress syndrome, and infrequently, myocarditis. Early diagnosis and prompt treatment are crucial in managing scrub typhus. Here, we present four cases of scrub typhus with a comprehensive literature review. This study highlights the significance of considering scrub typhus as a possible diagnosis in patients of all ages from endemic regions who exhibit symptoms such as fever, thrombocytopenia, or transaminitis, even in the absence of typical clinical features. Two cases exhibited the characteristic lesion of eschar at the site of mite feeding. One case involved a middle-aged woman who was diagnosed with typhus-induced myocarditis with left ventricular dysfunction. Another case involved a 23-day-old neonate with poor feeding and seizures, who was diagnosed with late-onset sepsis with meningitis. Scrub typhus was confirmed in all cases using a positive qualitative IgM ELISA. However, it is preferred to use paired (ELISA before and after antibiotic therapy) or quantitative titers for confirmation. Healthcare providers must consider the patient's exposure history and clinical presentation to diagnose and treat scrub typhus promptly.

Guidelines for Diagnosis and Management of Infective Endocarditis in Adults: A WikiGuidelines Group Consensus Statement.

Importance: Practice guidelines often provide recommendations in which the strength of the recommendation is dissociated from the quality of the evidence. Objective: To create a clinical guideline for the diagnosis and management of adult bacterial infective endocarditis (IE) that addresses the gap between the evidence and recommendation strength. Evidence Review: This consensus statement and systematic review applied an approach previously established by the WikiGuidelines Group to construct collaborative clinical guidelines. In April 2022 a call to new and existing members was released electronically (social media and email) for the next WikiGuidelines topic, and subsequently, topics and questions related to the diagnosis and management of adult bacterial IE were crowdsourced and prioritized by vote. For each topic, PubMed literature searches were conducted including all years and languages. Evidence was reported according to the WikiGuidelines charter: clear recommendations were established only when reproducible, prospective, controlled studies provided hypothesis-confirming evidence. In the absence of such data, clinical reviews were crafted discussing the risks and benefits of different approaches. Findings: A total of 51 members from 10 countries reviewed 587 articles and submitted information relevant to 4 sections: establishing the diagnosis of IE (9 questions); multidisciplinary IE teams (1 question); prophylaxis (2 questions); and treatment (5 questions). Of 17 unique questions, a clear recommendation could only be provided for 1 question: 3 randomized clinical trials have established that oral transitional therapy is at least as effective as intravenous (IV)-only therapy for the treatment of IE. Clinical reviews were generated for the remaining questions. Conclusions and Relevance: In this consensus statement that applied the WikiGuideline method for clinical guideline development, oral transitional therapy was at least as effective as IV-only therapy for the treatment of IE. Several randomized clinical trials are underway to inform other areas of practice, and further research is needed.

Vaccine Derived Poliovirus (VDPV).

Poliomyelitis is caused by Poliovirus, a member of a large group of enteroviruses. Vaccine-derived polioviruses (VDPVs) stem from mutated live poliovirus, which is contained in the Oral Polio Virus vaccine (OPV). In addition, the emergence of VDPV is one of the global challenges for the eradication of poliomyelitis. VDPVs continue to affect different parts of the world; 1081 cases occurred in 2020 and 682 cases in 2021. There are several reasons that may have caused the increase in circulating vaccine-derived poliovirus (cVDPV) after the "switch" from the trivalent to the bivalent oral polio vaccine. One reason is the low vaccination rate among the targeted population, which has been further aggravated by the COVID-19 pandemic. Several strategies could control the spread of VDPV including the use of the monovalent OPV (mOPV-2). The risk of VDPV can be minimized through increased immunization rates and the use of safer vaccine alternatives. The global effort to eradicate polio has made significant progress over the years, but continued vigilance and investment in immunization programs are needed to achieve the ultimate goal of a polio-free world.

Prevalence of active and passive smoking among asthma and asthma-associated emergency admissions: a nationwide prevalence survey study.

Asthma affects 7% of children and 8% of adults in the United States. There is a paucity of studies examining the association between passive smoking and an increased risk of asthma exacerbations that led the authors to examine the association between various modes of smoking and rates of asthma exacerbations. A retrospective cross-sectional/case-control study was conducted using the National Health and Nutrition Examination Survey dataset (2013-2018). Out of 312,979 respondents, 35,758 (11.43%) had a history of asthma, 9083 (2.9%) had asthma attacks in the past year, and 4731 (1.51%) had asthma-related emergency room admissions in the past year. Prevalence of asthma-related emergency admissions were higher among active cigarette smoking (46.25 vs 35.46%), e-cigarette smoking (26.63 vs 16.07%), and passive smoking at home (37.53 vs 25.67%), workplace passive smoking (14.35 vs 12.11%), in bar (32.38 vs 26.16%), and car (26.21 vs 14.44%) (p < 0.0001). In multivariate regression analysis, we found regular cigarette smoking (OR 1.13, 95% confidence interval (CI) 1.009-1.260, p = 0.0252), e-cigarette (OR 2.13, 95% CI 1.92-2.36, p = 0.0043), cigar use (OR 1.21, 95% CI 1.1-1.33, p < 0.001), ultra-long cigarette length (OR 4.85, 95% CI 3.33-7.06, p < 0.0001), and passive smoking (OR 5.25, 95% CI 3.43-8.06, p < 0.0001) were associated with increased rates of asthma exacerbations over last 12 months. The study shows increased odds of asthma exacerbations among those using ultra-long cigarettes, e-cigarettes, and cigars. Consequently, passive inhalation from even a single smoker in the home, workplace, bars and cars is associated with worsening outcomes in asthma patients.

E-cigarette use and prevalence of lung diseases among the U.S. population: a NHANES survey.

The primary aim of this study was to evaluate epidemiological characteristics and prevalence of lung disease among e-cigarettes users in the United States. A population-based, cross-sectional survey was performed using the National Health and Nutrition Examination Survey (NHANES) of 2015-2018. Adults using e-cigarettes (SMQ900), traditional smoking (SMQ020: > 100 cigarettes in lifetime or SMQ040: current cigarettes use), and dual smoking (e-cigarettes and traditional smoking) were identified and compared in their sociodemographic characteristics and prevalence of lung diseases (Asthma: MCQ010 and COPD: MCQ160O). We used the chi square test (categorical variables) and Mann-Whitney test and unpaired-student t test (continuous variables). p-value <0.05 was used as a reference. We excluded respondents <18 years and missing data on demographics and outcomes. Out of 178,157 respondents, 7745 (4.35%), 48,570 (27.26%), and 23,444 (13.16%) were e-cigarette smokers, traditional smokers, and dual smokers, respectively. Overall prevalence of asthma was 15.16% and COPD was 4.26%. E-cigarette smokers were younger in comparison to traditional smokers (median: 25 years vs 62 years; p < 0.0001). In females (49.34% vs 37.97%), Mexican (19.82% vs 13.35%), annual household income above $100,000 (23.97% vs 15.56%), prevalence of e-cigarette smoking was higher in comparison to traditional smoking (p < 0.0001). The prevalence of COPD was higher among dual smokers in comparison to e-cigarette and traditional smoking (10.14% vs 0.25% vs 8.11%; p < 0.0001). Prevalence of asthma was higher among dual and e-cigarette smokers in comparison with traditional smokers and non-smokers (22.44% vs 21.10% vs 14.46% vs 13.30%; p < 0.0001). Median age (Q1-Q3) was lower at which asthma (7 years (4-12) vs 25 years (8-50)) was diagnosed first among e-cigarettes smokers in comparison with traditional smokers. In a mixed effect multivariable logistic regression analysis, we found higher odds of asthma among e-cigarette users in comparison with non-smokers (Odds ratio (OR): 1.47; 95% Confidence Interval (CI): 1.21-1.78; p = 0.0001). Chronic Obstructive Pulmonary Disease (COPD) respondents were also associated with 11.28 higher odds of e-cigarette utilization (Oddsratio (OR): 11.28; 95% Confidence Interval (CI): 5.59-22.72; p < 0.0001). We conclude the higher prevalence of e-cigarette users is seen among the younger population, female, Mexican race, and annual income above $100,000 in comparison to traditional smokers. Chronic Obstructive Pulmonary Disease (COPD) and asthma were both more prevalent in dual smokers. As asthma was more prevalent and diagnosed at an early age in e-cigarette smokers, more prospective studies are needed to understand the effects of e-cigarette among the population at risk to mitigate the sudden rise in utilization and to create awareness.

Unmasking the Common Thief: A Rare Cause of Isolated Hypoglossal Nerve Palsy.

Multiple cranial nerve palsies frequently accompany hypoglossal nerve palsy, potentially indicating malignancy, such as lymphoma, nasopharyngeal carcinoma, or metastases. However, when solely the hypoglossal nerve is affected, the causes may involve Chiari malformation, arachnoid cyst, or infectious mononucleosis, suggesting a positive prognosis. Craniocervical junction tuberculosis (TB), is an uncommon cause of isolated hypoglossal nerve palsy and has been reported infrequently in the literature. Craniocervical junction tuberculosis accounts for only 0.5% of TB cases overall and 6% of extra-pulmonary TB cases. We present here one such case of a 17-year-old male of Indian origin with a subacute history of tongue deviation and neck pain. Additionally, the patient reported loss of weight and appetite. The patient had significant posterior cervical lymphadenopathy. Neurological examination revealed findings suggestive of right peripheral hypoglossal nerve involvement. Blood investigations showed lymphocytosis along with an elevated erythrocyte sedimentation rate of 45 mm/h and elevated lactate dehydrogenase levels of 325 U/L. Tuberculin skin testing was positive and sputum acid-fast staining confirmed acid-fast bacilli. Magnetic Resonance Imaging of the cervical spine revealed a soft tissue component in the prevertebral space measuring 3.5×4.8 cm with a right paraspinal component adjoining the hypoglossal canal with peripheral contrast enhancement. Histological findings on the lymph node showed granulomatous lymphadenitis, suggestive of tuberculosis. The patient was started on 4-drug anti-tubercular therapy consisting of Isoniazid, Rifampicin, Pyrazinamide, and Ethambutol for a period of 18 months. He was subsequently followed up for 6 months till the resolution of palsy. This case emphasizes the importance of thorough evaluation and a meticulous workup to identify the underlying cause of hypoglossal nerve palsy and the importance of considering tuberculosis as a potential cause of isolated hypoglossal nerve palsy in everyday practice.

Can Moxidectin Be an Anthelmintic Alternative for Trichuris trichiura and Strongyloides stercoralis: A Systematic Review.

Strongyloides stercoralis and Trichuris trichiura parasitic infections are two of the many neglected tropical diseases. These parasitic infections are of considerable public health relevance, particularly in resource-limited countries. Moxidectin, a well-established drug in veterinary medicine, is now a Food and Drug Administration (FDA) approved medication for human onchocerciasis. For the past five years, this medication has been under clinical trials to evaluate its efficacy and safetiness in other helminthic infections. Moxidectin might complement the already existing treatment and control of soil-transmitted helminthiasis (STH). Therefore, we systematically reviewed existing human interventional studies to evaluate the efficacy and safety of this medication when administered alone or in combination with other antiparasitic medications in order to achieve a cure.

Programmed Death-Ligand 1 (PD-L1) Positivity and Factors Associated with Poor Prognosis in Patients with Gastric Cancer: An Umbrella Meta-Analysis.

Gastric cancer (GC) is one of the most common malignancies throughout the world with late diagnosis and poor prognosis. The expression of programmed death-ligand 1 (PD-L1) in GC is attributed to immune evasion and tumor progression. PD-L1 positivity has both predictive and prognostic biomarker potential. Aiming to summarize a large amount of research and to provide a definitive conclusion to the conflicting results on the prognostic significance of PD-L1 expression in GC, we performed an umbrella review based on existing meta-analyses which were published recently (2016-2021) and indexed in the PubMed database. Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was used in August 2021 to screen articles, and data extraction with quality assessment was performed on the selected meta-analyses. Review Manager (RevMan) 5.3 software was used to analyze the HR and OR with a 95% confidence interval (CI) among PD-L1 positive GC patients. We also assessed the between-study heterogeneity (I 2). Forest and Funnel plots were obtained, and a P-value of <0.05 was considered statistically significant. A total of 567 articles were screened, and we selected three meta-analyses with a total of 40 studies conducted over a period of 14 years. In our umbrella review, a total of 8,419 GC patients with an average PD-L1 positivity of 39% were analyzed. We found that PD-L1 positivity in GC patients is associated with poor prognosis (pooled HR =1.44, 95% CI: 1.24-1.68, P<0.00001) having higher mortality reducing the chances of overall survival (OS). However, there are no significant differences in PD-L1 expression among different lymph node (LN) metastases (OR=1.31, 95% CI: 0.98-1.74, P=0.07) and tumor, node, and metastasis (TNM) stages (OR=1.13, 95% CI: 0.80-1.58, P=0.50). Early identification of PD-L1 expression may help tailor cost-effective and targeted immunotherapy among GC patients. More research is needed to further understand how PD-L1 affects LN metastasis and tumor invasion.

Implication of the emergence of the delta (B.1.617.2) variants on vaccine effectiveness.

INTRODUCTION: COVID-19 vaccines have been developed to compact the current SARS-CoV-2 pandemic and have been administered to people all over the world. These vaccines have been quite effective in reducing the possibility of severe illness, hospitalization and death. However, the recent emergence of Variants of Concern specifically the delta variant, B.1.617.2, had resulted in additional waves of the pandemic. METHODS: We aim to review the literature to understand the transmission and disease severity, and determine the efficacy of the current COVID-19 vaccines. We searched Pubmed, Scopus, and Embase till August 4th 2021, and used the search terms "delta variant", "vaccinations"," breakthrough infections", and "neutralizing antibody". For the meta-analysis, 21 studies were screened in particular and five articles (148,071 cases) were included in the study, and only four were analyzed in the meta-analysis. RESULTS: In this review, both in vitro and in vivo studies showed significant reductions in neutralization rates against delta variants for vaccinated individuals and convalescent patients with prior history of COVID-19. However, There was a lower incidence of infection with SARS-CoV-2 due to Delta variant was found after the second dose of Pfizer-BioNTech, Oxford-AstraZeneca and Moderna vaccines. CONCLUSION: In fully vaccinated individuals, symptomatic infection with the delta variant was significantly reduced, and therefore, vaccinations play an important role to assist the fight against delta variant.

Antibiotics in the pipeline: a literature review (2017-2020).

INTRODUCTION: Antimicrobial resistance (AMR) is an emerging global threat. It increases mortality and morbidity and strains healthcare systems. Health care professionals can counter the rising AMR by promoting antibiotic stewardship and facilitating new drug development. Even with the economic and scientific challenges, it is reassuring that new agents continue to be developed. METHODS: This review addresses new antibiotics in the pipeline. We conducted a review of the literature including Medline, Clinicaltrials.org, and relevant pharmaceutical companies for approved and in pipeline antibiotics in phase 3 or new drug application (NDA). RESULTS: We found a number of new antibiotics and reviewed their current development status, mode of action, spectra of activity, and indications for which they have been approved. The included studies from phase 3 clinical trials were mainly utilized for the treatment of acute bacterial skin and skin structure infections, community-acquired bacterial pneumonia, and pneumonia acquired in the healthcare settings. The number of these agents is limited against high priority organisms. The identified antibiotics were based mainly on previously known molecules or pre-existing antimicrobial agents. CONCLUSION: There are a limited number of antibiotics against high priority organisms such as multi-drug-resistant Pseudomonas aeruginosa, and carbapenem-resistant Enterobacteriaceae. New antimicrobial agents directed against the top priority organisms as classified by the World Health Organization are urgently needed.

Post-acute COVID-19 syndrome (PCS) and health-related quality of life (HRQoL)-A systematic review and meta-analysis.

There is an established literature on the symptoms and complications of COVID-19 but the after-effects of COVID-19 are not well understood with few studies reporting persistent symptoms and quality of life. We aim to evaluate the pooled prevalence of poor quality of life in post-acute COVID-19 syndrome (PCS) and conducted meta-regression to evaluate the effects of persistent symptoms and intensive care unit (ICU) admission on the poor quality of life. We extracted data from observational studies describing persistent symptoms and quality of life in post-COVID-19 patients from March 10, 2020, to March 10, 2021, following PRISMA guidelines with a consensus of two independent reviewers. We calculated the pooled prevalence with 95% confidence interval (CI) and created forest plots using random-effects models. A total of 12 studies with 4828 PCS patients were included. We found that amongst PCS patients, the pooled prevalence of poor quality of life (EQ-VAS) was (59%; 95% CI: 42%-75%). Based on individual factors in the EQ-5D-5L questionnaire, the prevalence of mobility was (36, 10-67), personal care (8, 1-21), usual quality (28, 2-65), pain/discomfort (42, 28-55), and anxiety/depression (38, 19-58). The prevalence of persistent symptoms was fatigue (64, 54-73), dyspnea (39.5, 20-60), anosmia (20, 15-24), arthralgia (24.3, 14-36), headache (21, 3-47), sleep disturbances (47, 7-89), and mental health (14.5, 4-29). Meta-regression analysis showed the poor quality of life was significantly higher among post-COVID-19 patients with ICU admission (p = 0.004) and fatigue (p = 0.0015). Our study concludes that PCS is associated with poor quality of life, persistent symptoms including fatigue, dyspnea, anosmia, sleep disturbances, and worse mental health. This suggests that we need more research on PCS patients to understand the risk factors causing it and eventually leading to poor quality of life.

Demographics and Clinical Characteristics of Adult Patients Hospitalized due to COVID-19 in a Rural/Suburban Integrated Health System in Southcentral Pennsylvania, March Through May 2020.

Existing characterizations of coronavirus disease 2019 (COVID-19) admissions have occurred primarily in urban settings. This report describes demographic and clinical characteristics of the first COVID-19 patients presenting to a 6-hospital integrated health care system in rural/suburban southcentral Pennsylvania. Medical records of adult patients admitted with COVID-19 between March and May of 2020 were retrospectively reviewed for demographics, symptomatology, imaging, and lab values. Results were largely consistent with previous studies, although gastrointestinal manifestations were more prevalent, with diarrhea reported in 25.4% of patients hospitalized due to COVID-19. Nursing home patients represented 10.1% of admissions but accounted for 35.5% of total deaths in our sample. Patients self-identifying as Hispanic were disproportionately affected. Although Hispanic ethnicity was self-reported in only 9% of the community population, Hispanic patients accounted for 34% of admissions. Our data provide a unique focused review of hospitalized COVID-19 patients in a rural/suburban setting.

Anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines: a systematic review and meta-analysis.

BACKGROUND: Currently there is no systematic review and meta-analysis of the global incidence rates of anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines in the general adult population. OBJECTIVES: To estimate the incidence rates of anaphylactic and nonanaphylactic reactions after COVID-19 vaccines and describe the demographic and clinical characteristics, triggers, presenting signs and symptoms, treatment and clinical course of confirmed cases. DESIGN: A systematic review and meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] statement was followed. METHODS: Electronic databases (Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, and Nature) were searched from 1 December 2020 to 31 May 2021 in the English language using the following keywords alone or in combination: anaphylaxis, non-anaphylaxis, anaphylactic reaction, nonanaphylactic reaction, anaphylactic/anaphylactoid shock, hypersensitivity, allergy reaction, allergic reaction, immunology reaction, immunologic reaction, angioedema, loss of consciousness, generalized erythema, urticaria, urticarial rash, cyanosis, grunting, stridor, tachypnoea, wheezing, tachycardia, abdominal pain, diarrhea, nausea, vomiting and tryptase. We included studies in adults of all ages in all healthcare settings. Effect sizes of prevalence were pooled with 95% confidence intervals (CIs). To minimize heterogeneity, we performed sub-group analyses. RESULTS: Of the 1,734 papers that were identified, 26 articles were included in the systematic review (8 case report, 5 cohort, 4 case series, 2 randomized controlled trial and 1 randomized cross-sectional studies) and 14 articles (1 cohort, 2 case series, 1 randomized controlled trial and 1 randomized cross-sectional studies) were included in meta-analysis. Studies involving 26,337,421 vaccine recipients [Pfizer-BioNTech (n = 14,505,399) and Moderna (n = 11,831,488)] were analyzed. The overall pooled prevalence estimate of anaphylaxis to both vaccines was 5.0 (95% CI 2.9 to 7.2, I2 = 81%, p = < 0.0001), while the overall pooled prevalence estimate of nonanaphylactic reactions to both vaccines was 53.9 (95% CI 0.0 to 116.1, I2 = 99%, p = < 0.0001). Vaccination with Pfizer-BioNTech resulted in higher anaphylactic reactions compared to Moderna (8.0, 95% CI 0.0 to 11.3, I2 = 85% versus 2.8, 95% CI 0.0 to 5.7, I2 = 59%). However, lower incidence of nonanaphylactic reactions was associated with Pfizer-BioNTech compared to Moderna (43.9, 95% CI 0.0 to 131.9, I2 = 99% versus 63.8, 95% CI 0.0 to 151.8, I2 = 98%). The funnel plots for possible publication bias for the pooled effect sizes to determine the incidence of anaphylaxis and nonanaphylactic reactions associated with mRNA COVID-19 immunization based on mRNA vaccine type appeared asymmetrical on visual inspection, and Egger's tests confirmed asymmetry by producing p values < 0.05. Across the included studies, the most commonly identified risk factors for anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines were female sex and personal history of atopy. The key triggers to anaphylactic and nonanaphylactic reactions identified in these studies included foods, medications, stinging insects or jellyfish, contrast media, cosmetics and detergents, household products, and latex. Previous history of anaphylaxis; and comorbidities such as asthma, allergic rhinitis, atopic and contact eczema/dermatitis and psoriasis and cholinergic urticaria were also found to be important. CONCLUSION: The prevalence of COVID-19 mRNA vaccine-associated anaphylaxis is very low; and nonanaphylactic reactions occur at higher rate, however, cutaneous reactions are largely self-limited. Both anaphylactic and nonanaphylactic reactions should not discourage vaccination.

Examining the Clinical Prognosis of Critically Ill Patients with COVID-19 Admitted to Intensive Care Units: A Nationwide Saudi Study.

Backgroundand Objectives: COVID-19 is a novel infectious disease caused by a single-stranded RNA coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We aimed to conduct a nationwide multicenter study to determine the characteristics and the clinical prognostic outcome of critically ill COVID-19 patients admitted to intensive care units (ICUs). Materials and Methods: This is a nationwide cohort retrospective study conducted in twenty Saudi hospitals. Results: An analysis of 1470 critically ill COVID-19 patients demonstrated that the majority of patients were male with a mean age of 55.9 ± 15.1 years. Most of our patients presented with a shortness of breath (SOB) (81.3%), followed by a fever (73.7%) and a cough (65.1%). Diabetes and hypertension were the most common comorbidities in the study (52.4% and 46.0%, respectively). Multiple complications were observed substantially more among non-survivors. The length and frequency of mechanical ventilation use were significantly greater (83%) in the non-survivors compared with the survivors (31%). The mean Sequential Organ Failure Assessment (SOFA) score was 6 ± 5. The overall mortality rate of the cohort associated with patients that had diabetes, hypertension and ischemic heart disease was 41.8%. Conclusion: Age; a pre-existing medical history of hypertension, diabetes and ischemic heart disease; smoking cigarettes; a BMI ≥ 29; a long mechanical ventilation and ICU stay; the need of ventilatory support; a high SOFA score; fungal co-infections and extracorporeal membrane oxygenation (ECMO) use were key clinical characteristics that predicted a high mortality in our population.

Efficacy and Toxicity of Fexinidazole and Nifurtimox Plus Eflornithine in the Treatment of African Trypanosomiasis: A Systematic Review.

Human African trypanosomiasis (HAT), or sleeping sickness disease, is an infection caused mainly by Trypanosoma brucei gambiense-human African trypanosomiasis (g-HAT) and is transmitted by tsetse flies. The disease goes through two stages: hemolymphatic and meningo-encephalic phases. The treatment for the second stage has changed from melarsoprol or eflornithine to nifurtimox-eflornithine combination therapy (NECT) and fexinidazole. We aimed to systematically review the literature on the efficacy and toxicity of fexinidazole and NECT. We used PubMed advanced strategy and Google Scholar databases, including clinical trials and observational studies on humans in the last 20 years in the English literature. Applying the inclusion/exclusion criteria, we reviewed eight studies. We used Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) and Meta-analysis of Observational Studies in Epidemiology (MOOSE) protocol. For assessing bias, we used the Cochrane Collaboration's tool for risk assessment of the clinical trials and the Robins-I tool for the observational studies. Overall, the clinical trials showed that NECT was non-inferior to eflornithine. The proportion of patients discharged alive is higher in patients treated with NECT vs. patients treated with eflornithine. Gastrointestinal complaints are a common side effect of NECT therapy, while fearful but relatively rare convulsions can also occur. The main limitation among the studies of NECT was the lack of blinding because most of them were open-label. Fexinidazole, the new oral medication showed is effective and safe for the treatment of g-HAT infection. Because of their convenience, fexinidazole is preferred over NECT therapy, oral vs. IV infusion in the first and second stages of the disease. Compared to older therapies, fexinidazole and NECT are more effective and safer than eflornithine and melarsoprol monotherapy.

An Adrenocortical Carcinoma Evolving After Nine Years of Latency From a Small Adrenal Incidentaloma.

Adrenal incidentalomas (AIs) are common incidental findings in medical practice with clinical significance. Although most AIs are nonsecretory and nonmalignant, they require a short course of follow-up over one to two years to rule out malignancy or hormonal secretion according to clinical practice guidelines. However, this can result in some adrenocortical carcinomas (ACCs) being missed if they transform at a later stage or evolve slowly. Here, we report one such case of an AI, which although remained indolent, eventually transformed into an ACC many years after the initial detection.

Crimean-Congo Hemorrhagic Fever Beyond Ribavirin: A Systematic Review.

Crimean-Congo hemorrhagic fever (CCHF) is a tick-borne virus endemic to a vast geographical area spanning from Africa to the shores of the Mediterranean Sea and north to the Balkans. The infection carries a high case fatality rate, which prompts the development of new treatment and prophylactic measures. This review explores the different treatment and prophylactic measures found in recent literature. For this purpose, we used Medical Subject Headings (MeSH) as well as PubMed advanced search. The inclusion criteria included full-text studies conducted on humans and in the English language. We found that plasma exchange was associated with a decrease in mortality rates. Similarly, the use of immunoglobulins proved effective in decreasing the severity and mortality risk. Ribavirin use was determined as a post-exposure prophylaxis drug with no statistically significant difference in oral or intravenous routes of administration. More studies should be conducted on CCHF as the number of outbreaks and endemic areas seem to be on the rise. For the time being, supportive therapy along with adjuvant antivirals appear to be the main course of management of CCHF. However, the need for definitive therapeutic agents and guidelines is warranted.

Mortality risk stratification helps identify patients with COVID-19 at risk of adverse outcomes.

Mortality risk stratification can identify patients with COVID-19 who are at higher risk of mortality, discharge to skilled nursing facility, and readmission, and may benefit from focused intervention strategies.