Smoking habits predict adverse effects after mRNA COVID-19 vaccine: Empirical evidence from a pilot study.

OBJECTIVES: The aim of this research was to investigate the possible association between smoking habits and the incidence of adverse effects (AEs) after mRNA COVID-19 vaccine. STUDY DESIGN: A longitudinal observational study was conducted on a sample of Italian healthcare workers. METHODS: Healthcare workers who were administered the mRNA COVID-19 vaccine (either BNT162b2 or mRNA-1273) were evaluated for the occurrence of AEs after three vaccine doses. Multivariate Poisson regression analyses were fitted to predict AE risk according to smoking characteristics - such as number of tobacco cigarettes smoked per day, smoking time, and use of electronic cigarette (e-cig). RESULTS: Of 320 total participants, 72 (22.5%) smoked cigarettes, and 50 (15.6%) used e-cig, 49 of which being dual users. Tobacco smoking significantly increased the risks of muscle and joint pain during the primary COVID-19 vaccination cycle and of chills during the whole vaccination series. The number of cigarettes smoked per day and vaping variously predicted AE onset during the whole cycle, with a tendency to respectively reduce and increase their risks. Duration of smoking did not affect any AE, except for headache after the booster dose. Most results remained significant after Bonferroni adjustment of significance level. CONCLUSION: Our pilot study indicated a possible effect of smoking habits on AE onset. Our research offers evidence that helps understanding possible predictors of the interindividual variability in COVID-19 vaccine response, serving as a reference for further studies on the effect of smoking on vaccine safety and effectiveness.

A double blind randomized controlled trial investigating efficacy and safety of varenicline for smoking cessation in patients with type 2 diabetes: study protocol.

Reducing exposure to cigarette smoke is an imperative for public health and for diabetic patients. Patients with diabetes who continue to smoke face challenges at quitting and the delivery of effective smoking cessation interventions is a major unmet need. The high-affinity α4ß2 nicotinic acetylcholine receptor partial agonist varenicline in combination with counseling is effective for smoking cessation, but evidence in patients with diabetes is limited. A clinical trial of varenicline targeted specifically at smokers with T2DM is warranted. This randomized, double blind, placebo-controlled trial will be the first study to test efficacy and safety of varenicline in smokers with type 2 diabetes mellitus (T2DM) over the course of 52 weeks. We hypothesize that varenicline treatment (1 mg BID, administered for 12 weeks) would increase quit rates, maintain smoking abstinence up to 1 year after treatment, and be well-tolerated in T2DM smokers intending to quit. Efficacy end points will include carbon monoxide-confirmed continuous abstinence rate (CAR) and 7-day point prevalence of abstinence. The results of this RCT will help inform medical/health authorities and physicians worldwide whether an optimally varenicline-treated cohort of T2DM patients who smoke will experience significant success rates, without significant side effects.Trial registration NCT01387425 ( https://clinicaltrials.gov/ct2/show/NCT01387425 ).

Smoking and diabetes: dangerous liaisons and confusing relationships.

The combined harmful effects of cigarette smoking and hyperglycemia can accelerate vascular damage in patients with diabetes who smoke, as is well known. Can smoking cause diabetes? What are the effects of smoking on macro and microvascular complications? Now growing evidence indicates that regular smokers are at risk of developing incident diabetes. Since the prevalence rates of smoking in patients with diabetes are relatively similar to those of the general population, it is essential to address the main modifiable risk factor of smoking to prevent the onset of diabetes and delay the development of its complications. Quitting smoking shows clear benefits in terms of reducing or slowing the risk of cardiovascular morbidity and mortality in people with diabetes. Does quitting smoking decrease the incidence of diabetes and its progression? What are the effects of quitting smoking on complications? The current evidence does not seem to unequivocally suggest a positive role for quitting in patients with diabetes. Quitting smoking has also been shown to have a negative impact on body weight, glycemic control and subsequent increased risk of new-onset diabetes. Moreover, its role on microvascular complications of the disease is unclear. What are the current smoking cessation treatments, and which ones are better for patients with diabetes? Stopping smoking may be of value for diabetes prevention and management of the disease and its macrovascular and microvascular complications. Unfortunately, achieving long-lasting abstinence is not easy and novel approaches for managing these patients are needed. This narrative review examines the evidence on the impact of smoking and smoking cessation in patients with diabetes and particularly in type 2 diabetes mellitus and its complications. In addition, management options and potential future directions will be discussed.

Conservative surgical treatment in rectal cancer after complete pathological response to neoadjuvant treatment. Prospective observational study.

In 2012 we started a prospective observational study at San Giovanni Addolorata Hospital in Rome for patients with rectal cancer with complete response to neoadjuvant therapy (nCRT). In our, IRB approved protocol, patients are evaluated at time 0 by physical, endoscopic, pathological and radiological examinations. 6 weeks after completion of nCRT they are re-evaluated. In case of persistence or progression of disease patients undergo surgery with Total Mesorectal Excision. In case of complete or major clinical response they are re-evaluated at 12 weeks and subjected to transanal surgical excision to confirm complete pathological response (pCR). If tumor is found in the transanal excision specimen the patient is operated upon whereas patients with pCR are followed up at 3 months interval.

Faldaprevir for the treatment of hepatitis C.

Enormous progress has been made in the understanding of the hepatitis C virus and the development of novel therapeutic agents since the identification of the virus, from initial interferon monotherapy to PEGylated interferon in combination with ribavirin for 48-72 weeks that used to be the standard of care in hepatitis C virus therapy. However, this combination has limited efficacy and a significant side effect profile including flu-like symptoms, anemia, leukopenia, autoimmune disorders and depression, so it is often poorly tolerated. Recently, direct-acting antiviral agents, such as the first-generation NS3/4A protease inhibitors, have been added to this combination, improving the percentage of successful treatments. Faldaprevir is a first-generation, second wave, protease inhibitor that, when combined with PEGylated interferon and ribavirin, has been shown to increase treatment success with shorter treatment duration. Various direct-acting antiviral agent combinations in interferon-free regimens have been effective in over 95% of patients and are now in licensed use.

Adenocarcinomas of appendix: a rare tumor. Two case reports.

Primary Adenocarcinomas of the appendix are rare tumor. Most commonly diagnosis was made after surgical pocedure of appendicectomy for suspect acute appendicitis and the pathology report confirms appendiceal neoplasm. Laboratory exams and imaging show low sensibility and specificity for preoperative diagnosis. We report two cases of primary mucinous adenocarcinoma in caucasian men misdiagnosed as having acute appendicitis. Appendicectomy was done and excised appendix was sent for histopathological examination. Mucinous Adenocarcinoma of the appendix was confirmed after histopathological examination. Right hemicolectomy, peritonectomy and Intraoperative Hyperthermic Chemotherapy were done as a second stage procedure. The surgical treatment of these neoplasms depends from the histological stage and local presentation. Cytoreductive surgery associated with Intraoperative Hyperthermic Chemotherapy show best results in advanced cases.

Effect of a nicotine-free inhalator as part of a smoking-cessation programme.

Smoking-cessation drugs are inadequate at addressing the behavioural component of tobacco dependence. Nicotine-free inhalators are plastic devices that may provide a coping mechanism for conditioned smoking by replacing some of the rituals associated with smoking gestures. This study assessed the effect of using a nicotine-free inhalator to improve success in a cessation programme. At baseline, 120 smokers attending a smoking-cessation programme were assessed for their sociodemographic factors, smoking history, depression, physical and behavioural dependence, and motivation. Participants were randomly assigned to two groups, nicotine-free inhalator group (PAIPO; Echos Srl, Milan, Italy) versus reference group. For the whole sample, no significant difference was found in quit rates at 24 weeks between the PAIPO group and the reference group. However, the quit rate in the PAIPO group (66.7%) was more than three-fold higher than the reference group (19.2%) for those individuals with high Glover-Nilsson Smoking Behavioural Questionnaire (GN-SBQ) scores at baseline. The results of the logistic model analysis indicate that a high GN-SBQ score is a strong independent predictor for successful quitting at 24 weeks (OR 8.88; 95% CI 2.08-37.94) in the PAIPO group. Nicotine-free inhalators may be beneficial when used in the context of smoking-cessation interventions, particularly for those smokers for whom handling and manipulation of their cigarettes plays an important part in the ritual of smoking.

[The impact of air pollution on health. The "Programme de Surveillance Air et Santé 9 villes" (Air and Health surveillance program in 9 cities)]. / Retentissement de la pollution atmosphérique sur la santé. Le Programme de Surveillance Air et Santé 9 villes.

OBJECTIVES: To quantify the short term effects of air pollution on mortality and hospitalisation for cardiovascular or respiratory disorders in the nine French cities (Bordeaux, Le Havre, Lille, Lyon, Marseille, Paris, Rouen, Strasbourg and Toulouse) of the Surveillance Air et Santé program. METHODS: Data were available on mortality and hospitalisation were available, respectively, from 1990 to 1997 and 1995 to 1999. Exposure data were the concentrations of sulphur dioxide, particles with a diameter of less than or equal to 10 mm, black smoke, nitrogen dioxide, ozone, and carbon monoxide. The analysis assessed the relationships, in each of the cities, between the daily numbers of deaths and hospitalisations and the daily levels of polluting agents, taking into account confounding factors. A combined relative risk was calculated for all the cities. The number of deaths and hospitalisations attributable to air pollution was then estimated for each of the cities, based on the relative risk. RESULTS: Significant relationships were found for mortality, from whatever cause, and for hospitalisations for respiratory disorders in children aged under 15. If the levels of air pollution were reduced to 10 microg/m3 in the nine cities, 2800 premature deaths and 750 hospitalisations for respiratory disorders in children would be avoided, every year. CONCLUSION: Today, it is possible to assess the benefits of reducing air pollution in terms of health in the short term. These analyses would provide a sanitary dimension to the strategies for the reduction of urban pollution on local and European level.

[Intraoperative limphonodal mapping in gastric, pulmonary and large bowel tumors. The sentinel limphonode technique]. / Mappatura linfonodale intraoperatoria in tumori gastrici, polmonari e del grosso intestino. La tecnica del linfonodo sentinella.

The concept of the sentinel lymphatic node was introduced by Cabanas in 1977, but it has proved to be successful for the treatment of the melanoma and breast cancer only since the 90s. Many studies have recently extended this technique to other neoplasias. This study deals with 36 patients who were to undergo surgery for 14 gastric adenocarcinomas, 11 of the colon and 11 pulmonary. Once the neoplastic mass was detected, 2 to 5 ml of a vital dye (Blu Patent) were injected in the serosa along the perimeter of the tumor by means of several 0.5 ml injections. A lymphatic node was diagnosed in 22 patients, respectively 10 gastric neoplasias, 6 pulmonary, 6 of the colon. In 14 cases the lymphatic node was found to be negative, in 8 cases positive. In the remaining 14 patients the lymphatic node was not detected. Although data do not always agree, the sentinel lymphatic node technique seems to have been successful for this kind of tumors. For this reason we have carried out this study and published our first data.

Color vision and occupational toluene exposure.

We examined the relationship between acquired color vision loss and exposure to toluene and total hydrocarbons among 125 male workers. Seventy-two toluene-exposed printers were compared with 34 workers from the same photogravure plant with ambient background exposure, and with 19 workers from a bookbinding plant located in the same town (nonexposed). Environmental mean toluene exposure level at workstation was estimated from individual 8-h sampling. Historic exposure data from the last 30 years were used to construct two cumulative exposure indices, one for toluene and one for total hydrocarbons. Airborne toluene levels were overall lower than the current Threshold Limit Value (TLV) of 50 ppm. Color vision was assessed by the Lanthony D-15 desaturated panel. Color vision loss was quantitatively established by the Color Confusion Index (CCI) and classified by type of acquired dyschromatopsia according to Verriest's classification. CCI was positively related to current airborne toluene levels, and cumulative exposure indices for toluene and total hydrocarbons (.18< or =r< or =.35). Odds ratios of acquired dyschromatopsia were significant for current airborne toluene, toluene, and total hydrocarbon past exposure (1.27 [1.02-1.58], 1.21 [1.04-1.39], 1.15 [1.02-1.31], respectively). In conclusion, this study suggests that the Lanthony D-15 desaturated panel detects early neurotoxic effects among workers exposed to toluene.

Vaccination with attenuated simian immunodeficiency virus by DNA inoculation.

Delivering attenuated lentivirus vaccines as proviral DNA would be simple and inexpensive. Inoculation of macaques with wild-type simian immunodeficiency virus strain mac239 (SIV(mac239)) DNA or SIV(mac239) DNA containing a single deletion in the 3' nef-long terminal repeat overlap region (nef/LTR) led to sustained SIV infections and AIDS. Injection of SIV(mac239) DNA containing identical deletions in both the 5' LTR and 3' nef/LTR resulted in attenuated SIV infections and substantial protection against subsequent mucosal SIV(mac251) challenge.

Poststreptococcal glomerulonephritis presenting as impending airway obstruction.

The presence of poststreptococcal glomerulonephritis in the pediatric patient remains a diagnostic challenge to the emergency physician. The variability of both patient presentation and laboratory parameters often obscures the diagnosis. We describe a child who presented to the emergency department with subglottic edema and the possibility of impending airway compromise. The child was admitted to the hospital under close observation, and several days later, the diagnosis of poststreptococcal glomerulonephritis was made.

Simian immunodeficiency virus infections in vervet monkeys (Clorocebus aethiops) at an Australian zoo.

A number of monkey species, including African green monkeys and African vervet monkeys (Chlorocebus aethiops), are frequently infected in the wild and in captivity with a Simian immunodeficiency virus strain, SIVagm, a primate lentivirus. Up to 50% of African green monkeys are estimated to be infected with SIVagm. SIV strains are very closely related to HIV-2 strains, which are a cause of AIDS in humans, predominantly in western Africa, although cases in Australia have also been reported. It is generally thought that SIV is non-pathogenic in several natural hosts, including African green monkeys. Nevertheless many SIV strains induce a profound immunodeficiency virtually identical to HIV-1 induced AIDS in humans when administered to Asian macaque species such as rhesus (Macaca mulatta) or pigtailed macaques (M nemestrina). SIV infection of Asian macaque species is frequently employed as an animal model for AIDS vaccine studies. In November 1996 a group of 10 African vervet monkeys were imported from the USA for display at Victoria's Open Range Zoo in Werribee. Two animals in this group of monkeys later developed a fatal gastroenteric illness. These diagnoses led us to initiate SIV testing of the colony.

A mutation in a mitochondrial transmembrane protein is responsible for the pleiotropic hematological and skeletal phenotype of flexed-tail (f/f) mice.

We have studied the flexed-tail (f) mouse to gain insight into mammalian mitochondrial iron metabolism. Flexed-tail animals have axial skeletal abnormalities and a transient embryonic and neonatal anemia characterized by pathologic intramitochondrial iron deposits in erythrocytes. Mitochondrial iron accumulation is the hallmark of sideroblastic anemias, which typically result from defects in heme biosynthesis or other pathways that lead to abnormal erythroid mitochondrial iron utilization. To clone the f gene, we used positional cloning techniques, and identified a frameshift mutation in a mitochondrial transmembrane protein. The mutated gene, Sfxn1, is the prototype of a novel family of evolutionarily conserved proteins present in eukaryotes.

Does selenium reduce the risk of threatened preterm delivery associated with placental cytochrome P450-1A1 activity?

Selenium (Se), an essential trace element in human nutrition, is thought to have an important role in the prevention of oxygen damage by organic hydroperoxides generated by oxidative metabolism. Epidemiological studies have shown an association between placental cytochrome P450-1A1 (CYP1) activity and threatened preterm delivery (TPD), and other experimental studies have shown alterations in fetal development with CYP1 activity or toxicity. The present study examined the possible protective effect of selenium on the potential toxicity of maternal exposure to polycyclic aromatic hydrocarbons (PAHs) on the normal course of pregnancy. Placental CYP1 activity was used as a risk factor resulting from maternal exposure to PAHs. TPD occurrence was used as a general indicator of troubles in the normal course of pregnancy. A group of TPD patients and a group of controls were selected from 178 pregnant women attending obstetrical care in a maternity hospital. Selenium concentrations in maternal plasma were lower in the TPD group: 63.7 ng/ml (CI 95% confidence bounds = 43.6-82.2) vs 69.2 ng/ml (CI 95% confidence bounds = 49. 3-96.3) (t test, P<0.01). When placental CYP1 was induced, an association between TPD and selenium was found, with an increase of 10 ng/ml for the latter. An adjusted odds ratio of 0.55 (CI 95% confidence bounds = 0.34-0.88; chi(2), P<0.01) was estimated. When placental CYP1 was not activated, the odds ratio was estimated at 0.99 (CI 95% confidence bounds=0.95-1.03; NS). This epidemiologic finding suggests that antioxidant Se status may be a protective factor against the potential toxic effect of PAHs on the normal course of pregnancy. The downward trend that we observed supports the hypothesis that the one-electron pathway metabolism of PAHs may explain a large fraction of TPD and some preterm deliveries.

The molecular defect in hypotransferrinemic mice.

Hypotransferrinemic (Trf(hpx/hpx)) mice have a severe deficiency in serum transferrin (Trf) as the result of a spontaneous mutation linked to the murine Trf locus. They are born alive, but before weaning, die from severe anemia if they are not treated with exogenous Trf or red blood cell transfusions. We have determined the molecular basis of the hpx mutation. It results from a single point mutation, which alters an invariable nucleotide in the splice donor site after exon 16 of the Trf gene. No normal Trf messenger RNA (mRNA) is made from the hpx allele. A small amount of mRNA results from the usage of cryptic splice sites within exon 16. The predominant cryptic splice site produces a Trf mRNA carrying a 27-base pair (bp), in-frame deletion. Less than 1% of normal levels of a Trf-like protein is found in the serum of Trf(hpx/hpx) mice, most likely resulting from translation of the internally deleted mRNA. Despite their severe Trf deficiency, however, Trf(hpx/hpx) mice initially treated with transferrin injections can survive after weaning without any further treatment. They have massive tissue iron overload develop in all nonhematopoietic tissues, while they continue to have severe iron deficiency anemia. Their liver iron burden is 100-fold greater than that of wild-type mice and 15- to 20-fold more than that of mice lacking the hemochromatosis gene, Hfe. Trf(hpx/hpx) mice thus provide an additional model with a defined molecular defect for the study of genetic iron disorders.

Negative relationships between erythrocyte Ca-pump activity and lead levels in mothers and newborns.

Lead poisoning induces hematological, gastrointestinal and neurological dysfunctions. One of the potential mechanisms is the inhibition of calcium-pump (Ca-pump), a transport protein. We investigated the effects of an environmental low lead exposure on Ca-pump activity in 247 mothers and their newborns. Maternal and cord blood, and newborn and mother hair, were sampled at delivery. Geometric means for mother and cord blood lead (Pb-B), and for mother and newborn hair lead (Pb-H), were 6.3 and 4.8 microg/dl, and 1.7 and 1.1 microg/g. Means for mother and cord basal Ca-pump activities were 2,442 and 2,675 nM/mg/hr. Mother enzymatic activity was negatively related to her Pb-B and Pb-H and to the cord Pb-B and newborn Pb-H levels. Newborn enzymatic activity was negatively related to his Pb-H level only. Adjustment for gestational age, child's sex, mother's age at delivery, alcohol, coffee and tea consumption, and smoking habits during pregnancy did not modify these relationships. Our findings support the hypothesis that lead toxicity could be in part mediated by a reduction of Ca-pump activity. This effect could be observed at low environmental exposure, in mothers and newborns.