All natural animals and plants are holobionts, consisting of the host and microbiome, which is composed of abundant and diverse microorganisms. Health and disease of holobionts depend as much on interactions between host and microbiome and within the microbiome, as on interactions between organs and body parts of the host. Recent evidence indicates that a significant fraction of the microbiome is transferred by a variety of mechanisms from parent to offspring for many generations. Genetic variation in holobionts can occur in the microbiome as well as in the host genome, and it occurs more rapidly and by more mechanisms in genomes of microbiomes than in host genomes (e.g. via acquisition of novel microbes and horizontal gene transfer of microbial genes into host chromosomes). Evidence discussed in this review supports the concept that holobionts with their hologenomes can be considered levels of selection in evolution. Though changes in the microbiome can lead to evolution of the holobiont, it can also lead to dysbiosis and diseases (e.g. obesity, diarrhea, inflammatory bowel disease, and autism). In practice, the possibility of manipulating microbiomes offers the potential to prevent and cure diseases.
This review examines the risk of developing celiac disease (CD) and other autoimmune diseases in individ¬uals receiving the rotavirus (RV) vaccine compared to the normal population. Celiac disease is a malabsorp¬tive, chronic, immune-mediated enteropathy involving the small intestine. The pathogenesis of CD is multifactorial, and mucosal immunity plays an important role in its development. Low mucosal IgA levels significantly increase the risk of developing the disease. Rotavirus is an infectious agent that causes diar¬rhea, particularly in children aged 0–24 months, and is frequently involved in diarrhea-related deaths in these children. An oral vaccine against RV has been developed. While it is effective on RV infection, it also contributes to increasing mucosal immunity. Studies have indicated that individuals immunized with the RV vaccine are at lower risk of developing CD than unvaccinated individuals. In addition, the mean age for developing CD autoimmunity may be higher in the vaccinated group than in controls receiving placebo. Additional studies that include children immunized with different RV vaccines and unvaccinated children would provide more meaningful results. Although current data suggest a possible association of RV vaccina¬tion with a reduced risk of developing CD and other autoimmune diseases, this remains an unanswered question that merits greater international investigation.
Objectives: To study the correlation between the putative cancer stem cell (CSC) markers aldehyde dehydrogenase 1 (ALDH1), cluster of differentiation 44 (CD44), sex-determining region Y-box 2 (SOX2), and octamer-binding protein 4 (OCT4) and human papilloma virus (HPV) infection using p16, the surrogate marker of HPV in oral epithelial dysplasia (OED) and normal mucosa.
Methods: Five sections each from 40 histopathologically diagnosed cases of different grades of OED and 10 cases of normal oral mucosa without dysplasia were immunohistochemically stained with p16, ALDH1, CD44, SOX2, and OCT4, respectively.
Results: Expression of ALDH1 and SOX2 was significantly increased in OED cases, whereas CD44 and OCT4 expression was increased in normal mucosa. P16-positive OED cases showed upregulation of ALDH1 and OCT4 expression as compared to p16-negative cases, while CD44 and SOX2 expression was downregulated in p16-positive OED cases; however, the results were not statistically significant.
Conclusion: The present study indicated a suggestive link between p16 and cancer stem cell marker expression in HPV-associated OED, and that p16 has a significant role in CSC progression in OED. This is the first study to evaluate the expression of putative CSC markers in HPV-associated OED. However, low study numbers are a potential limiting factor in this study.
Despite the wide endorsement of shared decision making (SDM), its integration into clinical practice has been slow. In this paper, we suggest that this integration may be promoted by teaching SDM not only to residents and practicing physicians, but also to undergraduate medical students. The proposed teaching approach assumes that SDM requires effective doctor–patient communication; that such communication requires empathy; and that the doctor’s empathy requires an ability to identify the patient’s concerns. Therefore, we suggest shifting the focus of teaching SDM from how to convey health-related information to patients, to how to gain an insight into their concerns. In addition, we suggest subdividing SDM training into smaller, sequentially taught units, in order to help learners to elucidate the patient’s preferred role in decisions about her/his care, match the patient’s preferred involvement in these decisions, present choices, discuss uncertainty, and encourage patients to obtain a second opinion.
Background: Eosinophils constitute 1%–5% of peripheral blood leukocytes, less in the presence of acute infections (referred to as eosinopenia). Studies indicate that eosinopenia can be used as a prognostic predictor for chronic obstructive pulmonary disease exacerbation, sepsis, or acute myocardial infarction disease. There are only a few studies about predicting mortality in emergency departments and intensive care units (ICUs). Prognostic studies about patients in ICUs are generally carried out using different scoring systems. We aimed to analyze if the eosinophil count can estimate the prognosis among non-traumatic patients who underwent cardiopulmonary resuscitation and were hospitalized in ICU thereafter.
Methods: The data were evaluated of 865 non-traumatic adult patients (>18 years of age) who were admitted with cardiopulmonary arrest or developed cardiopulmonary arrest during clinical follow-ups. Admission venous blood sample tests, complete blood count, and biochemical laboratory results were recorded. Arterial blood gas results were also evaluated. The mean results of the recorded laboratory results were compared between the surviving and non-surviving patients groups.
Results: There was a significant difference between the two groups in regard to platelet, eosinophil count, pH, PaO2, SaO2, and HCO3- (P<0.001 for all). In the multiple linear regression analysis, eosinophil counts were found to be an independent factor (odds ratio=0.03, 95% confidence interval 0.33–0.56, P<0.001) associated with the mortality after cardiopulmonary resuscitation.
Conclusion: Because admission eosinophil counts can be measured easily, they are inexpensive biomarkers that can be used for predicting the prognosis among the patients who have return of spontaneous circulation and are treated in ICUs.
Objective: This study examined the reliability of the various parameters obtained in diagnostic ureteroscopy for upper-tract urothelial carcinoma (UTUC) in predicting the degree of differentiation in the final pathological report after radical nephroureterectomy (RNU).
Methods: We conducted a retrospective review of patients undergoing RNU at a single tertiary hospital between 2000 and 2020. Only patients who underwent preoperative diagnostic ureteroscopy (URS) were included. The results of urine selective cytology, endoscopic appearance of the tumor, and biopsy taken during ureteroscopy were compared to the final pathological report.
Results: In total, 111 patients underwent RNU. A preliminary URS was performed in 54. According to endoscopic appearance, 40% of the “solid”-looking tumors were high grade (HG), while 52% of those with a papillary appearance were low grade (LG). Positive cytology predicted HG tumors in 86% of cases. However, 42% of patients with negative cytology had HG disease. The biopsies acquired during URS showed that HG disease findings matched the final pathology in 75% of cases. However, 25% of patients noted as being HG, based on URS biopsies, were noted to have LG disease based on nephroureterectomy biopsies. Full analyses revealed that 40% of the cases diagnosed as LG based on the URS biopsies actually had HG disease.
Conclusions: Direct tumor observation of papillary lesions, negative cytology, and biopsies indicating LG disease are of low predictive value for classifying the actual degree of tumor differentiation. No single test can accurately rule out HG disease. In light of the rising use of neo-adjuvant chemotherapy in UTUC, a reliable predictive model should be developed that accurately discriminates between HG and LG disease.
Background: Early thyroid cancers have excellent long-term outcomes, yet the word “cancer” draws unnecessary apprehension. This study aimed to define when the recommendations for observation and surveillance may be extended to early thyroid cancers at the population level.
Methods: Non-metastasized thyroid cancers ≤40 mm diameter were identified from the 1975–2016 Surveillance, Epidemiology and End Results (SEER) database. Causes of death were compared across demographic data. Disease-specific outcomes were compared to the age-adjusted healthy United States (US) population. Survival estimates were computed using Kaplan–Meier and compared using the Cox proportional hazard model. Dynamic benchmarks impacting disease-specific overall survival were determined by decision tree modeling and tested by the Cox model.
Results: Of the 28,728 thyroid cancers included in this study, 98.4% underwent some form of thyroid-specific treatment and were followed for a maximum of 10.9 years. This group had a 4.3% mortality rate at the end of follow-up (10.9 years maximum), with 13 times more deaths attributed to competing risks rather than thyroid cancer (stage T1a versus stage T1b, P=1.000; T1 versus T2, P<0.001). Among the untreated T1a or T1b tumors, the risk of disease-specific death was 21 times lower than death due to other causes. There was no significant difference between T1a and T1b tumors nor across sex. The age-adjusted risk of death for the healthy US population was higher than the population with thyroid cancer. Dynamic categorization demonstrated worsening outcomes up to 73 years, uninfluenced by sex or tumor size. For patients over 73 years of age, only tumors >26 mm impacted outcomes.
Conclusion: Based on the current data, T1a and T1b nodules have similar survival outcomes and are not significantly impacted even when left untreated. Multi-institutional prospective studies are needed to confirm these findings so that current observation and surveillance recommendations can be extended to certain T1 thyroid nodules.
Background: With the availability of coronavirus disease 2019 (COVID-19) vaccine, concerns have been raised regarding pre-vaccination seroprevalence in healthcare workers (HCW). This study examines the seroprevalence of HCW at an Israeli tertiary medical center before first BNT162b2 vaccination.
Methods: This was a retrospective observational study. Before vaccination, HCW at our center were offered serological testing. Data on their epidemiological, workplace, and quarantine history were collect¬ed. The SARS-CoV-2 IgG assay was performed pre-vaccination.
Results: A total of 4,519 (82.5%) of the HCW were tested. Of these, 210 were seropositive; 101 had no known history of COVID-19. Of the 101 asymptomatic HCW, only 3 (3%) had worked at COVID-19 depart¬ments, and 70 (69.3%) had not been previously quarantined. Positive serology was similarly distributed across age groups, and about 40% had no children. Nearly half of the HCW tested were administrative and service staff. Overall, seropositive tests were associated with having no children (OR 1.42, 95% CI 1.06–1.89; P=0.0218), history of having been quarantined without proof of disease (OR 6.04, 95% CI 4.55–8.01; P<0.001), and Arab ethnicity (OR 3.36, 95% CI 2.54–4.43; P<0.001). Seropositivity was also more prevalent in members of the administration compared to other sectors, medical and paramedical, who are exposed to patients in their daily work (OR 1.365, 95% CI 1.02–1.82; P=0.04).
Conclusions: The low percentage of asymptomatic COVID-19 among our HCW may reflect the high compliance to personal protective equipment use despite treating hundreds of COVID-19 patients. The relatively high number of childless seropositive HCW could reflect misconceptions regarding children as a main source of infection, leading to carelessness regarding the need for appropriate out-of-hospital protection.
Breast cancer is a common malignancy and a common cause of cancer-related mortality in women. Pre-treatment workup of breast cancer does not routinely include positron emission tomography scans. We aimed to review cases of women with breast cancer and a synchronous second primary malignancy. We present three cases of women with non-metastatic cancer in whom a synchronous second primary malignancy was found. Synchronous, second primary malignancies which were identified included rectal cancer, gastrointestinal stromal tumor, and non-small cell lung cancer. All second primary malignancies were identified by a PET-CT scan. In conclusion, PET-CT may be used for detection of secondary primary malignancies in select breast cancer patients.
Background: Transthyretin (TTR), also known as prealbumin, has been suggested as an indicator of protein and nutritional status.
Objective: The aim of this study was to examine the maternal and umbilical cord (UC) TTR in relation to intrauterine growth, and the serum TTR of preterm infants in relation to nutritional status and growth.
Methods: After application of exclusion criteria, 49 preterm infants (mean gestational age and birth-weight 32.9±2.9 weeks and 1822±556 g) were included in the study. Transthyretin was sampled at birth and on days 14, 28 or at discharge with growth parameters and nutritional laboratories.
Results: Mean UC and maternal TTR were positively correlated (8.5±2.4 mg/dL and 20.4±7.0 mg/dL, r=0.31, P=0.07). Umbilical cord TTR was neither an index of maturity nor of intrauterine growth. Umbilical cord TTR was higher in females (9.4±2.6 versus 7.6±1.8 mg/dL, P=0.015). Maternal TTR was lower in twin pregnancies (16.8±4.9 versus 22.5±7.3 mg/dL, P=0.007). Although TTR levels gradually increased over time in correlation with post-menstrual and chronological ages (r=0.24, P=0.011 and r=0.40, P<0.001, respectively), there was no correlation to weight gain (r=0.10, P=0.41), nutritional status, protein intake, or laboratories. The only significant correlations were between TTR and glucose and triglycerides levels (r=0.51, P<0.001 for both).
Conclusions: Although TTR levels increased over time, we could not demonstrate significant correlations between TTR and indices of the nutritional status in preterm infants at birth or during the neonatal course.
