Comparative Outcomes of Treatment Modalities in Nonagenarians with Nonmetastatic Pancreatic Adenocarcinoma.

INTRODUCTION: There has been a rise in the elderly patient population seeking care for pancreatic ductal adenocarcinoma (PDAC). We aim to delineate the effectiveness of therapeutic options in nonagenarians (age 90-99 years) diagnosed with resectable PDAC. METHODS: We utilized the National Cancer Database to identify patients with nonmetastatic PDAC (stage I-III) from 2004-2021. The study compared median overall survival (mOS) using Kaplan-Meier curves among five treatment categories: surgery, surgery along with chemoradiation, chemotherapy alone, radiotherapy alone, and chemoradiation alone. Cox Proportional Hazard was used in multivariable analyses. RESULTS: Of 459,174 patients, 793 aged ≥90 had nonmetastatic PDAC. Of these, 245 (30.9%) patients underwent chemotherapy alone, 296 (37.3%) radiotherapy alone, 162 (20.4%) chemoradiation, 58 (7.3%) curative-intent resection, and 32 (4.0%) underwent surgery combined with chemoradiation. The mOS 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) (P<0.001) for chemoradiation. In multivariable analysis, odds of survival were better for surgery alone patients compared to chemotherapy alone patients, though they did not significantly differ compared to patients receiving radiotherapy alone or chemoradiation alone. Nonetheless, surgery combined with chemoradiation was associated with decreased mortality risk compared to surgery alone (HR: 0.46 [95% CI 0.25-0.87], P=0.02). Operative 30-day mortality was 8.8%, and 90-day mortality was 17.8%. CONCLUSION: Surgery combined with chemoradiation improves survival among nonagenarians with PDAC as compared to other therapies. However, only 1 in 25 patients received all three treatment components. Secondly, our study highlights a very high operative mortality in nonagenarians.

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.

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.

Healthcare Workers' Knowledge and Attitude Toward Telemedicine During the COVID-19 Pandemic: A Global Survey.

Introduction Telemedicine is the utilization of communication technologies to provide healthcare services remotely. It has an increasingly pivotal role in enabling medical professionals to extend the provision of care to patients facing geographical barriers. The benefits of telemedicine have become more apparent during the coronavirus pandemic. To maximize its application, it is crucial to ascertain the understanding and attitudes of healthcare professionals toward its use. The aim of this study is to collect data and evaluate the current knowledge and perceptions of medical staff toward the use of telemedicine. Methods In this cross-sectional study, we conducted a global survey of 1091 healthcare workers. Data were collected through a questionnaire after an extensive literature review. Frequency, percentages, and cumulative percentages were calculated to portray the profile of the participants. Results Of the respondents, the majority had heard about (90.9%), witnessed (65.3%), or were familiar with (74.6%) how telemedicine is used in practice. Seventy-two point two percent (72.2%) were familiar with the tools that may be used in this technology. The familiarity with telemedicine was noted to be consistently higher in those with a medical degree and experience of less than five years. Furthermore, attitudes toward providing healthcare remotely were generally positive with 80% thinking that telemedicine reduced staff workload, 80.6% reporting that it reduces the unnecessary transportation cost, and 83% believing that it saves clinicians' time. However, 20% of respondents said that telemedicine increases staff workload and 40.5% of healthcare workers believed telemedicine threatens information confidentiality and patient privacy. Conclusion Although telemedicine is a novel and emerging practice in many countries, it appears to have a promising contribution to healthcare services. This is particularly important during a pandemic, as it ensures effective healthcare with the maintenance of social distancing measures. Moreover, the respondents of this study showed good knowledge and positivity in their attitude toward telemedicine.

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.

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.

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.

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.

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.

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.

Children in detention amidst COVID-19 in Africa: A wound untreated.

Children in detention in Africa are part of the vulnerable population exposed to the COVID-19 pandemic due to factors such as overcrowding, poor healthcare of inmates, and lousy state of the facilities. The number of children in detention was estimated to be about one million in 2010, and this has further increased threat to global health. The fall in operating criminal justice systems, from the aspect of rehabilitation and reform in Africa, to its being plagued with crisis, overpopulation, and inability to conform to fundamental human rights and health standards. It was noted that children in detention in Africa end up in prison mainly because they are either given birth to by incarcerated mothers or sentenced to jail based on their alleged criminal activity. Also, certain limitations in some African countries to track the prevalence of COVID-19 and other diseases include inaccessible data, non-specificity of data, and unreliable information regarding the current prison situation. Sometimes, these data could be insufficient and hard to comprehend, primarily if written in the local language. The efforts to resolve the untreated wounds of children in detention during COVID-19 are somewhat tricky. However, this paper identifies these limitations and proffers recommendations such as; the identification and implementation of strategies that support the continuity of child-centered services, prioritizing children for immediate release, and ensuring adequate protection of their health and well-being, among others.

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.

Targeting Oxidative Stress Mechanisms to Treat Alzheimer's and Parkinson's Disease: A Critical Review.

Neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD) are becoming more frequent as the age increases. Contemporary therapies provide symptom resolution instead of targeting underlying pathological pathways. Consequently, there is considerable heterogeneity in response to treatment. Research has elucidated multiple potential of pathophysiological mechanisms contributing to neurodegenerative conditions, among which oxidative stress pathways appear to be suitable drug targets. The oxidative stress pathway has given rise to numerous novel pharmacological therapies that may provide a new avenue for neurodegenerative diseases. For example, SKQ (plastoquinone), MitoVitE, vitamin E, SOD mimic, MitoTEMPO (SOD mimetic), and bioactive molecules like curcumin and vitamin C have indeed been examined. To better understand how oxidative stress contributes to neurodegenerative diseases (such as Alzheimer's and Parkinson's), we analyzed the medicinal qualities of medicines that target markers in the cellular oxidative pathways. The specific pathway by which mitochondrial dysfunction causes neurodegeneration will require more investigation. An animal study should be carried out on medications that tackle cellular redox mechanisms but are not currently licensed for use in the management of neurodegenerative conditions.

Lipid Lowering Therapy: An Era Beyond Statins.

Dyslipidemia, specifically elevated low-density lipoprotein (LDL) cholesterol levels, causes atherosclerotic cardiovascular disease (ASCVD) and increases the risk of myocardial infarction and stroke. Statins, a class of drugs that exert their effects by inhibiting HMG-CoA reductase, a key enzyme in the synthesis of cholesterol, have been the mainstay of therapy for the primary prevention of cardiovascular disease and lipids reduction. Statins are associated with side effects, most commonly myopathy and myalgias, despite their proven efficacy. This review explores non-statin lipid-lowering therapies and examines recent advances and emerging research. Over the previous decades, several lipid-lowering therapies, both as monotherapy and adjuncts to statin therapy and lipid-targeting gene therapy, have emerged, thus redefining how we treat dyslipidemia. These drugs include Bile acids sequestrants, Fibrates, Nicotinic acid, Ezetimibe, Bempedoic acid, Volanesoren, Evinacumab, and the PCSK 9 Inhibitors Evolocumab and Alirocumab. Emerging gene-based therapy includes Small interfering RNAs, Antisense oligonucleotides, Adeno-associated virus vectors, CRISPR/Cas9 based therapeutics, and Non-coding RNA therapy. Of all these therapies, Bempedoic acid works most like statins by working through a similar pathway to decrease cholesterol levels. However, it is not associated with myopathy. Overall, although statins continue to be the gold standard, non-statin therapies are set to play an increasingly important role in managing dyslipidemia.

OMICs Technologies for Natural Compounds-based Drug Development.

Compounds isolated from natural sources have been used for medicinal purposes for many centuries. Some metabolites of plants and microorganisms possess properties that would make them effective treatments against bacterial infection, inflammation, cancer, and an array of other medical conditions. In addition, natural compounds offer therapeutic approaches with lower toxicity compared to most synthetic analogues. However, it is challenging to identify and isolate potential drug candidates without specific information about structural specificity and limited knowledge of any specific physiological pathways in which they are involved. To solve this problem and find a way to efficiently utilize natural sources for the screening of compounds candidates, technologies, such as next-generation sequencing, bioinformatics techniques, and molecular analysis systems, should be adapted for screening many chemical compounds. Molecular techniques capable of performing analysis of large datasets, such as whole-genome sequencing and cellular protein expression profile, have become essential tools in drug discovery. OMICs, as genomics, proteomics, and metabolomics, are often used in targeted drug discovery, isolation, and characterization. This review summarizes technologies that are effective in natural source drug discovery and aid in a more precisely targeted pharmaceutical approach, including RNA interference or CRISPR technology. We strongly suggest that a multidisciplinary effort utilizing novel molecular tools to identify and isolate active compounds applicable for future drug discovery and production must be enhanced with all the available computational tools.

Does Chronic Use of Steroids Affect Outcomes After Liver Resection? Analysis of a National Database.

INTRODUCTION: With the increasing age of patients, more patients on chronic preoperative steroids are undergoing liver resections. Our study aimed to assess the relationship between preoperative steroids and outcomes. METHODS: We performed a retrospective review of the 2014-2019 NSQIP database of all patients undergoing liver resections. Propensity score matching was utilized to match the two groups (chronic steroids vs. no steroids) based on demographics, preoperative laboratory data, and operative findings. The primary outcome measure was mortality. RESULTS: There were 712 patients in the chronic steroid group and 21,751 in the no steroid group. After propensity score matching; there were 420 patients in both groups. Post-match analysis again demonstrated that patients on chronic steroids were at higher risk of cardiac arrest than those not on steroids (OR 2.01, 95% CI 1.02-2.45, p = 0.04). In addition, rates of organ space wound infection (OR 2.66, CI 1.33-5.38, p = 0.03), superficial wound infection (OR 2.79, CI 1.08-5.41, p = 0.035), renal insufficiency (OR 1.25, CI 1.03-1.62, p = 0.02), postoperative sepsis (OR 1.28, CI 1.08-1.82, p = 0.04), DVT (OR 1.7, CI 1.01-2.82, p = 0.04), and bile leakage (OR 1.75, CI 1.24-3.36, p = 0.04) were also increased in patients on steroids. However, the matched cohorts were similar in postoperative mortality rates (OR 0.11, CI 0.6-1.17, p = 0.72). CONCLUSION: The study found higher morbidity rates in patients undergoing liver resections on chronic preoperative steroids but no differences in mortality.

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.