TGF-β and p53 Staining in CT-Guided and Endoscopic Ultrasound Fine-Needle Aspirates of Pancreatic Adenocarcinoma

Our purpose was to determine if fine-needle aspirates of pancreatic adenocarcinoma would produce material amenable to tumor marker staining and to correlate the expression of TGF-beta and p53 with patient and tumor data. One hundred twenty specimens were analyzed. TGF-beta was positive in 26% of cases and had no correlation with patient's age, sex, survival, stage, grade, or size. p53 was positive in 22% of the cases and correlated only with grade 1 tumors. Expression of TGF-beta and p53 can be tested on preserved cytologic specimens. This is the largest study to date correlating TGF-beta and p53 expression in pancreatic adenocarcinoma and patient demographics, prognosis, and tumor attributes. This is also the first study that did not select for surgical candidates. TGF-beta expression does not appear to have prognostic significance in pancreatic cancer. p53 was more common in well-differentiated tumors and may be an early mutation lost in more poorly differentiated tumors.     

Cost-Effectiveness of the Ponseti Method for Treatment of Clubfoot in Pakistan

Background

Clubfoot is disabling, with an incidence of 0.9/1,000 live births to 7/1,000 live births. It affects mobility, productivity, and quality of life. Patients are treated surgically or non-surgically using the Ponseti method. We estimated the cost per patient treated with both methods and the cost-effectiveness of these methods in Pakistan.

Methods

Parents of patients treated, either surgically or with the Ponseti method, at the Indus Hospital’s free program for clubfoot were interviewed between February and May 2012. We measured the direct and indirect household expenditures for pre-diagnosis, incomplete treatment, and current treatment until the first brace for Ponseti method and the first corrective surgery for surgically treated patients. Hospital expenditure was measured by existing accounts.

Results

Average per-patient cost was $349 for the Ponseti method and $810 for patients treated surgically. Of these, the Indus hospital costs were $170 the for Ponseti method and $452 for surgically treated patients. The direct household expenditure was $154 and $314 for the Ponseti and surgical methods, respectively. The majority of the costs were incurred pre-diagnosis and after inadequate treatment, with the largest proportion spent on transportation, material, and fee for service. The Ponseti method is shown to be the dominant method of treatment, with an incremental cost-effectiveness ratio of $1,225.

Conclusions

The Ponseti method is clearly the treatment of choice in resource-constrained settings like Pakistan. Household costs for clubfoot treatment are substantial, even in programs offering free diagnostics and treatments and may be a barrier to service utilization for the poorest patients.     

Analysis of Safety Margin of Lithium Carbonate Against Cardiovascular Adverse Events Assessed in the Halothane-Anesthetized Dogs

Lithium is one of the classical drugs that have been widely used for treating bipolar disorder. However, several cardiac side effects including sick sinus syndrome, bundle branch block, ventricular tachycardia/fibrillation, non-specific T-wave abnormalities in addition to Brugada-type electrocardiographic changes have been noticed in patients who were given antidepressant, anticonvulsant, and/or antipsychotic drugs besides lithium. In this study, we assessed cardiohemodynamic and electrophysiological effects of lithium carbonate by itself to begin to analyze onset mechanisms of its cardiovascular side effects. Lithium carbonate in intravenous doses of 0.1, 1, and 10 mg/kg over 10 min was cumulatively administered with an interval of 20 min to the halothane-anesthetized beagle dogs (n?=?4), which provided peak plasma Li⁺ concentrations of 0.02, 0.18, and 1.79 mEq/L, respectively, reflecting sub-therapeutic to toxic concentrations. The low and middle doses prolonged the ventricular effective refractory period at 30 min and for 5–30 min, respectively. The high dose decreased the heart rate for 45–60 min, delayed the intraventricular conduction for 15–20 min and the ventricular repolarization at 45 min, and prolonged the effective refractory period for 5–60 min. No significant change was detected in the other cardiovascular variables. Thus, lithium alone may have a wide safety margin against hemodynamic adverse events; however, it would directly and/or indirectly inhibit Na⁺ and K⁺ channels, which may synergistically increase the ventricular refractoriness from the sub-therapeutic concentration and decrease the heart rate at the supra-therapeutic one. These findings may partly explain its clinically observed various types of arrhythmias as well as electrocardiographic changes.     

Epidemiology of oral cancer in Arab countries

Objectives:

To review the oral cancer (OC) studies that were conducted in Arab countries with regard to epidemiology, risk factors, and prognosis.

Methods:

A computer-based PubMed literature search was performed to retrieve studies conducted in the Arab world on epidemiology of OC. After screening for exclusion criteria, cross-referencing, and searching local journals, a total of 19 articles were included.

Results:

Eight prevalence studies found an OC prevalence ranging from 1.8 to 2.13 per 100,000 persons. Oral cancer patients were mostly in their fifth to sixth decade of life, and the incidence in younger age was reported in some Arab countries. Yemenis have an alarming high prevalence of OC among people younger than 45 years. Eleven studies explored determinants or prognosis of OC. Behavioral determinants such as smokeless tobacco (Shamma and Qat), and cigarette smoking were strongly associated with OC. Alcohol drinking and solar radiation exposures were cited as possible risk factors. The most affected sites were tongue, floor of the mouth, and lower lip variations in the affected site were attributed to the socio-cultural behavior of the populations under study. Squamous cell carcinoma was the most frequently detected cancer, and usually patients were in late stages (III and IV) at the time of diagnosis.

Conclusion:

No solid evidence exists regarding the true OC prevalence/incidence in most Arab countries due to the lack of national cancer registries and population-based studies.Oral cancer (OC) is defined as a neoplasm involving the oral cavity, which begins at the lips and ends at the anterior pillars of the fauces.1 Globally, OC is reported to be the eighth most commonly diagnosed cancer with an annual incidence of >300,000 cases.2 Incidence and mortality of OC are higher in developing countries when compared with developed countries.2,3 Global prevalence of OC shows wide variation in the geographical distribution. For instance, OC prevalence in the Indian subcontinent was 25% of all new cancer cases.4 A noticeable increase in the prevalence of OC was noted in some industrial countries (namely, UK, Netherlands, and Denmark)5,6 whereas other industrial countries (namely, Germany, France, Italy, Hong Kong, and USA) reported a decrease in the prevalence of OC.7 In 2010, the World Health Organization (WHO) reported an OC mortality rate of approximately 2 per 100,000 in the Middle East, which is lower than that reported in India and the United States.8 Squamous cell carcinoma (SCC) comprises 90-95% of all OC malignancies. In oral squamous cell carcinoma (OSCC), regional metastasis is prevalent in at least 30% of cases.9 It develops mainly between the sixth and the seventh decades of life and occurrence in younger people (<40 years old) is rare.10,11 Oral squamous cell carcinoma accounts for 4 of all malignancies in male and 2% in female.12 Higher proportions of OSCC, in addition to an alarming rise in incidence among young people are being documented worldwide.5,13 The most frequently affected sites of OC in Western countries are ventro-lateral aspects of the tongue and floor of the mouth, accounting for more than 50% of cases.12 Conversely, in the southeastern part of the Asian continent, OC is significantly higher in buccal and commissural mucosa. This was attributed directly to the use of unrefined topical tobacco, being chewed or kept in the mouth for long periods.14 The etiology of OC is multi-factorial comprising genetic, social, behavioral, and environmental risk factors. The major etiologic factors in the genesis of OC are tobacco chewing and/or smoking, and alcohol consumption.15 Human papillomaviruses (HPVs) have been considered as etiologic agents, particularly in OC with no tobacco or alcohol association.16 Potentially malignant disorders often precedes OSCC, and those showing features of moderate or severe epithelial dysplasia carry the highest risk for malignant transformation.17The greatest challenge is that OC is not detected early enough for successful treatment, despite the fact that OC is mostly a visible lesion. Most dentists or general medical practitioners misdiagnose OC for more innocent lesions that show similar clinical appearance.18 The aim of this article is to summarize the OC studies that were conducted in the Arab countries in regard to epidemiology, risk factors, and prognosis.     

The impact of the COVID-19 pandemic on the mental health of healthcare workers: study protocol for the COVID-19 HEalth caRe wOrkErS (HEROES) study

Background

Preliminary country-specific reports suggest that the COVID-19 pandemic has a negative impact on the mental health of the healthcare workforce. In this paper, we summarize the protocol of the COVID-19 HEalth caRe wOrkErS (HEROES) study, an ongoing, global initiative, aimed to describe and track longitudinal trajectories of mental health symptoms and disorders among health care workers at different phases of the pandemic across a wide range of countries in Latin America, Europe, Africa, Middle-East, and Asia.

Methods

Participants from various settings, including primary care clinics, hospitals, nursing homes, and mental health facilities, are being enrolled. In 26 countries, we are using a similar study design with harmonized measures to capture data on COVID-19 related exposures and variables of interest during two years of follow-up. Exposures include potential stressors related to working in healthcare during the COVID-19 pandemic, as well as sociodemographic and clinical factors. Primary outcomes of interest include mental health variables such as psychological distress, depressive symptoms, and posttraumatic stress disorders. Other domains of interest include potentially mediating or moderating influences such as workplace conditions, trust in the government, and the country’s income level.

Results

As of August 2021, ~ 34,000 health workers have been recruited. A general characterization of the recruited samples by sociodemographic and workplace variables is presented. Most participating countries have identified several health facilities where they can identify denominators and attain acceptable response rates. Of the 26 countries, 22 are collecting data and 2 plan to start shortly.

Conclusions

This is one of the most extensive global studies on the mental health of healthcare workers during the COVID-19 pandemic, including a variety of countries with diverse economic realities and different levels of severity of pandemic and management. Moreover, unlike most previous studies, we included workers (clinical and non-clinical staff) in a wide range of settings.

     

The shared epitope hypothesis in rheumatoid arthritis: evaluation of alternative classification criteria in a large UK Caucasian cohort

OBJECTIVE: Many classification systems for the HLA-DRB1 allelic association with rheumatoid arthritis (RA) have been reported, but few have been validated in additional populations. We sought to evaluate 3 different DRB1 allele classification systems in a large cohort of Caucasian RA patients and control subjects in the UK. METHODS: HLA-DRB1 typing was undertaken in 1,325 Caucasian RA patients and 462 healthy Caucasian controls who were residents of the UK. Logistic regression analyses were performed to investigate the different classification systems. RESULTS: We confirmed the association between the susceptibility alleles S2 and S3P, as proposed by Tezenas du Montcel, and the presence of RA in UK Caucasians. A significant hierarchy of risk was observed within the S3P allele group. There was no evidence of a significant association between DRB1*1001 and RA. Our data did not support the hypothesis that an isoleucine at position 67 conferred protection against RA, other than in contrast to the susceptibility alleles. However, the presence of an aspartic acid at amino acid 70 did appear to confer some degree of protection. CONCLUSION: We were unable to fully substantiate any of the 3 recent revisions of the shared epitope hypothesis in this large cohort of Caucasian RA patients and control subjects in the UK. This reinforces the importance of evaluating disease susceptibility alleles in different Caucasian populations as well as in other ethnic groups. In particular, it will be important to clarify the precise DRB1 association in a given population before DRB1 genotyping is incorporated into clinical diagnostic or treatment algorithms.     

Bacteriological study of diabetic foot infections

AIMS: The polymicrobial nature of diabetic foot infection has been well documented in the literature. Patients with diabetic foot infection not exposed to antibiotics are not well studied before. The relative frequency of bacterial isolates cultured from community-acquired foot infections that are not exposed to antimicrobial agents for 30 days is studied. In addition, the bacterial comparative in vitro susceptibility to the commonly used antibacterial agents is assessed. METHODS: This is a prospective study in which the infected wounds of 86 consecutive diabetic patients seen in the diabetic foot clinic in Adan Teaching Hospital were cultured when visiting the clinic. The patients did not receive antimicrobial therapy 30 days prior to taking the cultures. The specimen was cultured using aerobic and anaerobic microbiological techniques. Isolates were tested for susceptibility to commonly used antimicrobial therapy. RESULT: Staphylococcus aureus was the most common isolate, being recovered from 38.4% of cases. Other organisms were Pseudomonas aeruginosa (17.5%) and Proteus mirabilis (18%), anaerobic gram-negative organisms (10.5%), mainly Bacteroides fragilis. Imipenem, meropenem, and cefepime were the most effective agents against gram-negative organisms. Vancomycin was the most effective against gram-positive organisms. CONCLUSION: S. aureus and P. aeruginosa were the most common causes of diabetic foot infections. Anaerobic organisms are still a common cause for infection, although the prevalence is less. These wounds may require use of combined antimicrobial therapy for initial management.