Seven classes of antiviral agents.

The viral epidemics and pandemics have stimulated the development of known and the discovery of novel antiviral agents. About a hundred mono- and combination antiviral drugs have been already approved, whereas thousands are in development. Here, we briefly reviewed 7 classes of antiviral agents: neutralizing antibodies, neutralizing recombinant soluble human receptors, antiviral CRISPR/Cas systems, interferons, antiviral peptides, antiviral nucleic acid polymers, and antiviral small molecules. Interferons and some small molecules alone or in combinations possess broad-spectrum antiviral activity, which could be beneficial for treatment of emerging and re-emerging viral infections.

Adverse fetal and neonatal outcomes following in-utero exposure to oxcarbazepine: A systematic review and meta-analysis.

AIM: This systematic review aims to assess the safety profile of oxcarbazepine during pregnancy. METHODS: Observational studies that included women who took oxcarbazepine anytime during pregnancy were included in our systematic review. The review did not include non-English articles, reviews, meta-analyses, case reports and animal studies. Different online sources such as MEDLINE, Cochrane library, Virtual Health Library, etc., were searched for published and unpublished literature. Assessment of the risk of bias in observational studies was carried out using the Newcastle-Ottawa Scale. The meta-analyses were performed using a random-effect model. GRADE was used for the evaluation of the quality of evidence for the primary outcomes. RESULTS: We included 19 cohort studies with a total of 5 071 137 patients, of which 2450 were exposed to oxcarbazepine either as monotherapy or polytherapy. The summary odds ratio (OR) was 1.69 (95% CI, 0.95-2.98) for congenital malformations following in-utero exposure to oxcarbazepine as compared to the control group of unexposed patients (seven studies [n = 625]), and was 1.19 (95% CI, 0.67-2.12) when compared to those following lamotrigine (LTG) exposure during pregnancy (3 studies [n = 591]). In total, three studies (n = 770) reported the association between in-utero oxcarbazepine exposure and fetal/perinatal deaths. The meta-analysis yielded a summary OR of 3.33 (95% CI, 1.70-6.51). CONCLUSION: Our systematic review will help healthcare providers and guideline developers regarding the treatment of epilepsy and other neurological disorders during pregnancy. More cohort studies with a higher sample size concerning oxcarbazepine use in pregnant patients are required to truly assess the in-utero safety profile of the drug.

Update of pathophysiology and treatment options of seborrheic keratosis.

Seborrheic keratosis (SK) is a common, benign tumor that can occur on everybody site and can be conservatively managed. Cosmetic concerns, especially when a lesion involves the facial area, are the most common reason for excision. SK shows male gender preponderance and increasing age is an independent association with the condition. Even though more prevalent in the elderly, it has also been reported in younger age groups like adolescents and young adults. Precise pathogenesis is still obscure, but ultra-violet exposure represents a predisposing factor to SK by altering the biochemical concentration and expression of factors like Glutamine deaminases, endothelin, and stem cell factor. Moreover, the accumulation of amyloid-associated protein has also been postulated. Involvement of genitalia has been associated with human papillomavirus infection. Recently, Merkel cell polyomavirus nucleic acid was also detected in SK. Several oncogenic mutations involving FGFR-3 and FOXN1 have been identified. SKs are usually classified clinically and histologically. Dermatoscopy is a noninvasive alternative diagnostic technique widely used in differentiating SK from other benign and malignant tumors. In terms of treatment, topical agents, shave dissection, cryosurgery, electrodesiccation, laser application and curettage under local anesthesia are safe methods for eradication of SKs, mostly for cosmetic purposes. Though generally safe, the latter techniques may occasionally cause post-procedure depigmentation, scarring, and recurrence. Nanosecond-pulsed electric field technology is a promising new technique with fewer side-effects.

National Trends in Cholecystectomy and Endoscopic Retrograde Cholangiopancreatography During Index Hospitalization for Mild Gallstone Pancreatitis.

BACKGROUND: Guidelines call for cholecystectomy during the index hospitalization for patients with gallstone pancreatitis. Therefore, the study sought to determine the trends for cholecystectomy and Endoscopic Retrograde Cholangiopancreatography (ERCP) for mild gallstone pancreatitis. METHODS: A retrospective analysis of the 2010-2018 Nationwide Readmission Database (NRD) was performed to identify patients with mild gallstone pancreatitis. The primary aim was to identify the trends in the use of cholecystectomy in these patients, and the secondary aim was to assess if ERCP alone was protective against readmission. RESULTS: A total of 510,470 patients with mild gallstone pancreatitis were identified. There has been an increasing trend in ERCP use (25% in 2018 vs. 22% in 2010; p-0.001) and a decline in cholecystectomy (37% in 2018 vs. 46% in 2010; p-0.001) prior to discharge. Multivariate analysis revealed higher 30-day readmission for patients who underwent ERCP without cholecystectomy (odds ratio1.3; 95% confidence interval, 1.1-3.5) during the index admission. CONCLUSIONS: There has been a decline in the use of cholecystectomy during index hospitalization for mild gallstone pancreatitis. In addition, ERCP was not protective against 30-day readmission from mild gallstone pancreatitis.

Chronic neutrophilic leukaemia and plasma cell-related neutrophilic leukaemoid reactions.

Many cases reported as 'chronic neutrophilic leukaemia' have had an associated plasma cell neoplasm. Recent evidence suggests that the great majority of such cases represent a neutrophilic leukaemoid reaction to the underlying multiple myeloma or monoclonal gammopathy of undetermined significance. We have analysed all accessible reported cases to clarify the likely diagnosis and to ascertain whether toxic granulation, Döhle bodies and an increased neutrophil alkaline phosphatase score were useful in making a distinction between chronic neutrophilic leukaemia and a neutrophilic leukaemoid reaction. We established that all these changes occur in both conditions. Toxic granulation and Döhle bodies are more consistently present in leukaemoid reactions but also occur quite frequently in chronic neutrophilic leukaemia. The neutrophil alkaline phosphatase score is increased in both conditions and is of no value in making a distinction.

Should myeloid and lymphoid neoplasms with PCM1-JAK2 and other rearrangements of JAK2 be recognized as specific entities?

Since the publication of the 2001 and 2008 World Health Organization classifications of tumours of haematopoietic and lymphoid tissues, there has been an increasing move towards classification of haematological neoplasms on the basis of the underlying molecular genetic disorder. In recent decades there have been a significant number of reports of haematological neoplasms with rearrangement of JAK2. Published data on such cases have therefore been analysed to determine if any specific entities could be identified. On the basis of this analysis, it is suggested that lymphoid and myeloid neoplasms associated with t(8;9)(p22;p24); PCM1-JAK2 fusion should be recognized as an entity. Furthermore, lymphoid and myeloid neoplasms associated respectively with t(9;12)(p24;p13); ETV6-JAK2 and with t(9;22)(p24;q11·2); BCR-JAK2 should be documented carefully in order to define their features more clearly and assess whether they can be recognized as entities. Identification of all these conditions is important because of the possibility of response to JAK2 inhibitors.

Does Preoperative Weight Loss Affect Outcomes After Major Liver Resection? Analysis of a National Database.

Introduction: The association between unintentional weight loss (WL) and outcomes after major hepatectomy for malignancy remains unclear.Methods: This retrospective cohort study reviewed the 2014-2019 NSQIP database of all patients who underwent major liver resections. The patients were categorized into two groups based on their history of weight loss. The primary outcome measure was the 30-day mortality. The secondary outcome was 30-day in-hospital complications.Results: In total, 384 patients had a history of preoperative weight loss. Preoperative WL was an independent predictor of septic shock (OR, 2.44; CI: 1.61, 3.69), bile leak (OR: 1.96; CI: 1.51, 2.55), and grade C liver failure (OR: 2.57; CI: 1.64, 4.01). However, preoperative WL was not a significant predictor of perioperative mortality (OR: 1.38; CI: 0.82, 2.32).Conclusion: The study found higher morbidity rates in patients undergoing liver resection with a history of weight loss. Further validation with prospective weight monitoring is needed to validate as a prognostic marker in patients undergoing hepatectomy. In addition, weight changes can help guide multidisciplinary decision-making in treating patients undergoing hepatectomy.

Comparative outcomes of treatment modalities in nonagenarians with nonmetastatic pancreatic adenocarcinoma.

BACKGROUND: There has been an increase in the elderly patient population seeking care for pancreatic ductal adenocarcinoma (PDAC). This study aimed to delineate the effectiveness of therapeutic options in nonagenarians (aged 90-99 years) diagnosed with resectable PDAC. METHODS: This study used the National Cancer Database to identify patients with nonmetastatic PDAC (stage I-III) from 2004 to 2021. The study compared median overall survival (mOS) using Kaplan-Meier curves among 5 treatment categories: surgery, surgery along with chemoradiation, chemotherapy alone, radiotherapy alone, and chemoradiation alone. Cox proportional hazards regression was used in multivariate analyses. RESULTS: Of 459,174 patients, 793 aged ≥ 90 years had nonmetastatic PDAC. Of 793 patients, 245 (30.9 %) underwent chemotherapy alone, 296 (37.3 %) underwent radiotherapy alone, 162 (20.4 %) underwent chemoradiation alone, 58 (7.3 %) underwent curative-intent resection, and 32 (4.0 %) underwent surgery combined with chemoradiation. The mOS estimates in different treatment modalities were 9.5 months (95 % CI, 6.7-14.5) for surgery alone, 19.1 months (95 % CI, 2.4-64.3) for surgery combined with chemoradiation, 8.2 months (95 % CI, 7.2-9.2) for chemotherapy alone, 8.4 months (95 % CI, 7.6-9.6) for radiotherapy alone, and 11.2 months (95 % CI, 8.7-12.9) for chemoradiation alone (P < .001). In multivariate analysis, the odds of survival were better for patients who underwent surgery alone than for those who underwent chemotherapy alone, although the odds of survival did not significantly differ between patients who underwent radiotherapy alone and those who underwent chemoradiation alone. Nonetheless, surgery combined with chemoradiation was associated with decreased mortality risk compared with surgery alone (hazard ratio, 0.46; 95 % CI, 0.25-0.87; P = .02). Operative 30-day mortality rate was 8.8 %, and 90-day mortality rate was 17.8 %. CONCLUSION: Surgery combined with chemoradiation improved the survival of nonagenarians with PDAC compared with other therapies. However, only 1 in 25 patients received all 3 treatment components. Moreover, our study highlights a very high operative mortality rate in nonagenarians.

Guillain-Barré syndrome following COVID-19 vaccination: An updated systematic review of cases.

Key Clinical Message: Guillain-Barré syndrome (GBS) is a rare but possible complication that may occur after COVID-19 vaccination. In this systematic review, we found that GBS presented in patients with an average age of 58. The average time for symptoms to appear was 14.4 days. Health care providers should be aware of this potential complication. Abstract: Most instances of Guillain-Barré syndrome (GBS) are caused by immunological stimulation and are discovered after vaccinations for tetanus toxoid, oral polio, and swine influenza. In this systematic study, we investigated at GBS cases that were reported after receiving the COVID-19 vaccination. Based on PRISMA guidelines, we searched five databases (PubMed, Google Scholar, Ovid, Web of Science, and Scopus databases) for studies on COVID-19 vaccination and GBS on August 7, 2021. To conduct our analysis, we divided the GBS variants into two groups, acute inflammatory demyelinating polyneuropathy and non-acute inflammatory demyelinating polyneuropathy (AIDP and non-AIDP), and compared the two groups with mEGOS and other clinical presentation In this systematic review, 29 cases were included in 14 studies. Ten cases belonged to the AIDP variant, 17 were non-AIDP (one case had the MFS variant, one AMAN variant, and 15 cases had the BFP variant), and the two remaining cases were not mentioned. Following COVID-19 vaccination, GBS cases were, on average, 58 years of age. The average time it took for GBS symptoms to appear was 14.4 days. About 56 percent of the cases (56%) were classified as Brighton Level 1 or 2, which defines the highest level of diagnostic certainty for patients with GBS. This systematic review reports 29 cases of GBS following COVID-19 vaccination, particularly those following the AstraZeneca/Oxford vaccine. Further research is needed to assess all COVID-19 vaccines' side effects, including GBS.

Outbreak of monophasic Salmonella Typhimurium Sequence Type 34 linked to chocolate products.

As of 3rd June 2022, 445 cases of monophasic Salmonella Typhimurium sequence type 34 infection had been reported globally. The outbreak was caused by two novel strains of monophasic S. Typhimurium with unusual multi-drug resistance. The majority of these cases involved children aged 10 or younger, and they had a hospitalization rate higher than most previous outbreaks of monophasic S. Typhimurium, but no fatalities were recorded. The infection was traced to certain Belgian chocolate products after extensive microbiological and epidemiological research. Public health officials took immediate action to recall all the contaminated products, and the risk of exposure was reduced. The common symptoms are bloody diarrhea, acute onset of fever, abdominal pain, and vomiting. This article aims to thoroughly review the recent outbreak of monophasic Salmonella Typhimurium ST-34, including its epidemiology and comparison with ongoing outbreaks. We also highlighted past chocolate-related salmonella outbreaks and current control and prevention guidelines and recommendations.

How common are taste and smell abnormalities in COVID-19? A systematic review and meta-analysis.

OBJECTIVE: Olfactory and gustatory dysfunction (OGD) are important early clinical symptoms of COVID-19. We aim to calculate the pooled prevalence of these symptoms and discuss the likely implications on clinical practice such as their use as screening tools and potential prognosis indicators. METHODS: Using a combination of keywords and medical subject headings, we searched for observational studies in the following five databases: Medline/PubMed, Scopus, Cochrane Library, Web of Science, and Google Scholar. Two authors independently screened and selected the final articles according to the inclusion criteria. Two investigators independently assessed the risk of bias in individual studies using the Newcastle-Ottawa Scale. Heterogeneity and publication bias were also assessed. The reported outcome of the pooled analysis was the prevalence of OGD calculated using a random-effect model. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed to report results. RESULTS: Seventeen studies with a total sample size of 4149 were included in this meta-analysis. Out of these, 2106 and 2676 patients reported some degree of olfactory and/or gustatory dysfunction with COVID-19, respectively. The reported outcomes were in terms of pooled prevalence, with gustatory dysfunction being 57.33% and olfactory dysfunction being 59.69%, a significantly high occurrence. CONCLUSION: There is a high occurrence of smell and taste impairment in COVID-19. Given the lack of objective testing for detecting OGD in most studies, the high prevalence found is likely to be an underestimation of the true prevalence. This implies that physicians must use them as reliable early indicators of COVID-19 and employ them before using expensive tests.

Radiation-induced coronary artery disease: a difficult clinical conundrum.

Accelerated coronary artery disease seen following radiation exposure is termed 'radiation-induced coronary artery disease' (RICAD) and results from both the direct and indirect effects of radiation exposure. Long-term data are available from survivors of nuclear explosions and accidents, nuclear workers as well as from radiotherapy patients. The last group is, by far, the biggest cause of RICAD presentation.The incidence of RICAD continues to increase as cancer survival rates improve and it is now the second most common cause of morbidity and mortality in patients treated with radiotherapy for breast cancer, Hodgkin's lymphoma and other mediastinal malignancies. RICAD will frequently present atypically or even asymptomatically with a latency period of at least 10 years after radiotherapy treatment. An awareness of RICAD, as a long-term complication of radiotherapy, is therefore essential for the cardiologist, oncologist and general medical physician alike.Prior cardiac risk factors, a higher radiation dose and a younger age at exposure seem to increase a patient's risk ratio of developing RICAD. Significant radiation exposure, therefore, requires a low threshold for screening for early diagnosis and timely intervention.

Pathobiology of Cutaneous Manifestations Associated with COVID-19 and Their Management.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19) has been a rising concern since its declaration as a pandemic by the World Health Organization on 11 March 2020. Recently, its association with multiple underlying organs has been identified that includes cardiac, renal, gastrointestinal, nervous systems, and cutaneous manifestations. Cutaneous COVID-19 findings have been supposedly classified into the following categories: vesicular (varicella-like), papulo-vesiculsar, chilblains-like ("COVID toes") maculopapular, and urticarial morphologies. In this review, we aim to focus on the proposed pathophysiology behind the various dermatological manifestations associated with COVID-19 and their associated management. We also included prevalence and clinical features of the different COVID-19-related skin lesions in our review. A comprehensive narrative review of the literature was performed in PubMed databases. Data from case reports, observational studies, case series, and reviews till June 2022 were all screened and included in the review.

Rise of syphilis surge amidst COVID-19 pandemic in the USA: A neglected concern.

Introduction: Syphilis is a treatable but highly contagious sexually transmitted disease (STI) that has a long history of infecting millions of people from diverse ethnicities and is mainly considered promiscuity. An uprise in syphilis cases is noted in the Coronavirus pandemic. This short communication discerns salient factors precipitating the syphilis upsurge, implications, current efforts, and recommendations. Discussion: A decrease in funds and investments for public health clinics during COVID-19 because the funds have been diverted for treating COVID-19 has resulted in a dramatic rise in syphilis. The main determinants of the increased spread of syphilis during the COVID-19 pandemic include unsafe sexual activities, reduced STI screening, lack of sufficient staff during the pandemic, and abandoning of STI programs and services. Recommendations: We recommend high-risk screening clinics and effective telehealth programs to combat against rising STI burden in the US.

Challenges faced by African healthcare workers during the third wave of the pandemic.

Africa experienced the third wave of the coronavirus disease in 2019, which caused an 18% rise in cases in most parts of the continent. As of January 2022, the region had an estimated 10.4 million cumulative cases and more than 233,000 deaths, which add up to the burden on the fragile healthcare system, which continues to face a shortage of staff and resources. In addition, the progression of the pandemic further threatens the supply of healthcare workers in Africa due to the increased risk of infection and death, where more than 10,000 healthcare workers in 40 countries have been infected with the virus. This is amid low vaccination coverage, with only 27% of healthcare workers in Africa being fully vaccinated against the disease. Despite the delayed start and slow progression of the pandemic in Africa, there are increasing concerns over the challenges on the African healthcare workers such as economic insecurity and stressful working conditions, which are associated with limited access to personal protective equipment and other vital resources such as ventilators. In addition, the pandemic further predisposes African healthcare workers to social stigma, burnout, insomnia, depression, and fear of safety in their families. The aim of this study is to highlight the challenges faced by African healthcare workers, provide recommendations for change, and emphasize the need to prioritize their physical and mental well-being.

Acute hepatitis of unknown origin in Europe-Adding fuel to already burning pandemic.

The rise in the cases of acute hepatitis of unknown aetiology in the paediatric population is a public health concern worldwide and investigations to ascertain the exact cause of this outbreak are being carried out extensively by the concerned authorities. In early April 2022, the World Health Organisation (WHO) issued a warning on acute hepatitis of unknown origin in children. Since then, there have been continuing additional reports of the cases globally. The recent cases of acute hepatitis of unknown aetiology are more prevalent in children aged <10 years, are more clinically severe, and a high percentage of infected individuals develop acute liver failure in contrast to the previous cases. The aetiology of this disease and its complete pathogenesis is still unclear. This review critically focuses on the current leading hypothesis and provides comprehensive information regarding this recent outbreak that can help in handling the situation by a better understanding of its aetiology.

Diagnostic Accuracy of Magnetic Resonance Spectroscopy in Predicting the Grade of Glioma Keeping Histopathology as the Gold Standard.

Background Gliomas are the most prevalent intrinsic tumors of the central nervous system and are categorized from grade I to grade IV. Magnetic resonance imaging (MRI) provides exact diagnosis, prognosis, and assessment of tumor response to current chemotherapy/immunotherapy and radiation therapy. With histopathology serving as the gold standard, we aimed to assess the diagnostic accuracy of magnetic resonance spectroscopy (MRS) in predicting glioma grade. Methodology This cross-sectional study was conducted in the Department of Radiology, KRL Hospital, Islamabad, from December 15, 2019, to September 30, 2021. After providing written consent, 80 patients with untreated gliomas were included in this study. The voxel of interest was identified using MRI brain conventional contrast-enhanced sequences to assess the grade of the gliomas and link it to the histology report. Following this identification, tissue metabolites were calculated using MRS. Results The patients' age ranged from 13 to 80 years, with a mean age of 49.5 years. Male patients comprised 57.5% of the total study population, while female patients comprised 42.5%. Overall, 23.75% of patients had low-grade tumors, while 76.25% had high-grade tumors. Low-grade tumors had a choline (Cho)/creatine (Cr) metabolite ratio of 1.7421, whereas high-grade tumors had an average Cho/Cr metabolite ratio of 2.5575. N-acetyl aspartate (NAA)/Cr ratio was 1.6368 in low grade and 0.6734 in high-grade tumors. Sensitivity of 77% and specificity of 84.2% were noted, with 78.75% diagnostic accuracy for the Cho/Cr ratio. Conclusions Multivoxel MRS has been shown to reliably predict the grade of gliomas despite its non-invasive nature and lack of procedural challenges. When used together Cho/Cr and NAA/Cr ratios and histopathology can accurately determine tumor grade and can be used as a supplementary non-invasive technique.

Terminal digit preference and the accuracy of breast cancer diameter reporting based on Benford's law.

Background: Breast cancer is the most frequent cancer in women all over the world, and it is one of the leading causes of cancer-related deaths in women. A pathologist's partiality for the last digit of a patient's name can lead to errors in the measurement of malignancies. This means that, rather than recording the exact measurement of a tumor, a pathologist might round it off to his preferred terminal digit. Methods: It is a retrospective cross-sectional study in which data on primary tumor resection for 1000 breast cancer patients was obtained from KRL Hospital's patient directory from November 2016 to December 2020. The tumors were measured in cm to one decimal point along their longest dimension. Ki-67 markers were used to categorize the tumors into nine categories. Terminal digit preference was evaluated using Benford's law. Results: The recording of the Ki-67 index revealed evidence of pentameric preference. The numbers three, five, and six appeared more frequently in the histogram of the Ki-67 index distribution measured in percentage. The frequency of nine dropped dramatically. However, the influence of tumor size terminal digits on Ki-67 staining scores (low proliferative vs high proliferative) assessed using the Mann-Whitney U Test demonstrated that tumor size terminal digits had no significant effect on Ki-67 staining scores (p = 0.114). Conclusion: The Ki-67 index shows evidence of pentameric preference for digits three, five, and six. The frequency of nine has dropped dramatically. The influence of tumor size on terminal digits on staining scores (low proliferative vs. high proliferative) was assessed using the Mann-Whitney U Test.