Hematologic Malignancies Diagnosed in the Context of the mRNA COVID-19 Vaccination Campaign: A Report of Two Cases.

BACKGROUND: During the last two years, the COVID-19 pandemic led to millions of disease-related deaths worldwide. The efforts of the scientific community facing this global challenge resulted in outstanding achievements. Thus, within one year, new mRNA-based vaccines against SARS-CoV-2 viral infection were released, providing highly efficient protection and showing a very good safety profile in the general population. However, clinical data collection after vaccination is a continuous process for the long-term safety of any new medical product. The aim of our paper is to present two cases of hematological malignancies: diffuse large B-cell non-Hodgkin lymphoma and T/NK-cell lymphoma, diagnosed shortly after the administration of the mRNA COVID-19 vaccine. METHODS AND RESULTS: Case 1: A female patient was admitted with a suspicious cervical mass that emerged within one week after the administration of second dose of the BNT162b2 COVID-19 vaccine. Surgical removal followed by pathology assessment of the specimen confirmed the diagnosis of diffuse large B-cell non-Hodgkin lymphoma. Case 2: A male patient was admitted with multiple ulcerative oral lesions arising on the third day after the initial dose of the BNT162b2 COVID-19 vaccine. These lesions had a progressive character and during the following months were complicated with repetitive episodes of heavy oral bleeding, requiring blood transfusions. The incisional biopsy of the lesions and pathological assessment of the specimens confirmed the diagnosis of T/NK-cell lymphoma. CONCLUSIONS: The safety profile of the mRNA-based vaccines is an undeniable fact. In most cases, suspicions of potentially aggressive side effects were ruled out, proving to be transient post-vaccine reactions. Clinicians should remain alert to report any potentially aggressive manifestations emerging in the context of mRNA COVID-19 vaccination, such as these cases of hematological malignancies, in order to promote additional investigations on the particular mechanisms of action of COVID-19 vaccines and to provide the best medical care to the patients.

Non-Alcoholic Fatty Liver Disease in HIV/HBV Patients - a Metabolic Imbalance Aggravated by Antiretroviral Therapy and Perpetuated by the Hepatokine/Adipokine Axis Breakdown.

Non-alcoholic fatty liver disease (NAFLD) is strongly associated with the metabolic syndrome and is one of the most prevalent comorbidities in HIV and HBV infected patients. HIV plays an early and direct role in the development of metabolic syndrome by disrupting the mechanism of adipogenesis and synthesis of adipokines. Adipokines, molecules that regulate the lipid metabolism, also contribute to the progression of NAFLD either directly or via hepatic organokines (hepatokines). Most hepatokines play a direct role in lipid homeostasis and liver inflammation but their role in the evolution of NAFLD is not well defined. The role of HBV in the pathogenesis of NAFLD is controversial. HBV has been previously associated with a decreased level of triglycerides and with a protective role against the development of steatosis and metabolic syndrome. At the same time HBV displays a high fibrogenetic and oncogenetic potential. In the HIV/HBV co-infection, the metabolic changes are initiated by mitochondrial dysfunction as well as by the fatty overload of the liver, two interconnected mechanisms. The evolution of NAFLD is further perpetuated by the inflammatory response to these viral agents and by the variable toxicity of the antiretroviral therapy. The current article discusses the pathogenic changes and the contribution of the hepatokine/adipokine axis in the development of NAFLD as well as the implications of HIV and HBV infection in the breakdown of the hepatokine/adipokine axis and NAFLD progression.

Eosinophilic Colitis and Clostridioides difficile Sepsis With Rapid Remission After Antimicrobial Treatment; A Rare Coincidence and Its Pathogenic Implications.

Eosinophilic colitis is a rare inflammatory disorder of the digestive tract with chronic evolution and unknown pathophysiological mechanisms. The article describes the case of a 64-year old woman with a history of asthma and hypereosinophilia, who presented to a surgical department for persistent abdominal pain in the past 4 months, weight loss and malabsorption. She was diagnosed with eosinophilic colitis based on the colonoscopic result indicating extensive eosinophilic infiltration of the colonic mucosa correlated with the laboratory data and abdominal CT scan results. Following the colonoscopy, the patient developed fever, hypotension and diarrhea and was transferred to an Infectious Diseases Department with a presumptive diagnosis of abdominal sepsis. Treatment with ertapenem was immediately started. Metronidazole was also added due to a PCR positive stool test for Clostridioides difficile toxins encoding-genes. The patient displayed a rapid remission of the fever and of the intestinal complaints following antibiotic therapy and was discharged after 14 days. During a 3 months follow-up, the patient remained asymptomatic with normal values of laboratory parameters except for a persistent hypereosinophilia. The case outlines two distinguishing features: a histopathologic diagnosis of eosinophilic colitis, a rare diagnosis of a patient with chronic abdominal pain and an unexpected and rapid remission of the eosinophilic colitis following the antibiotic treatment and the restoration of the intestinal eubiosis.

Correlation of Caries Prevalence, Oral Health Behavior and Sweets Nutritional Habits among 10 to 19-Year-Old Cluj-Napoca Romanian Adolescents.

Background and objectives: The primary oral disease during adolescence is dental caries. Less is known about the caries prevalence, oral health behavior, and sweets nutritional habits in Romanian adolescents. The objective of this study was to assess the actual caries prevalence among Romanian adolescents in a representative area of Romania, Cluj, and to correlate with oral hygiene behaviors and dietary sugary foods intake. Materials and methods: We have done a cross-sectional study of 650 adolescents aged 10 to 19-years-old (average age 15.3 ± 2.8). We performed the oral dental examination according to the WHO methodology, calculated the number of decayed, missing (due to caries), and filled teeth (DMFT index), assessed the oral hygiene and dietary behaviors using a two-section valid questionnaire and statistically analyzed the interrelation between DMFT, oral hygiene and eating behaviors by multivariate statistical analysis. Results: (a) The caries prevalence in the adolescent population enrolled in the study was 95.5%; (b) the mean DMFT was 3.13 ± 2.0, without significant differences between the urban and rural adolescents (p = 0.253); lower in females than males (p < 0.050), (c) more than one third (33.7%, n = 219) of teenagers are seldom or never brush their teeth in the evening; (c) 40.6% of adolescents are missing the regular annual dental check-ups leading to an increased DMFT as shown in the multivariate analysis (p = 0.038); and (d) there is an increased prevalence of caries with age (p = 0.020), and with sugary sweetened beverages consumption (p = 0.028). Conclusions: Our study evidenced a persistent high caries prevalence in Romanian teenagers. Their dietary habits and irregular dental check-up were associated with the occurrence of dental conditions.

Ibalizumab Targeting CD4 Receptors, An Emerging Molecule in HIV Therapy.

The HIV infection is responsible for the most devastating global pandemic of the last century. More than 39 million people have died of HIV/AIDS since 1981. The development of the antiretroviral (ARV) treatment begins with the discovery of zidovudine a nucleoside reverse transcriptase inhibitor. This breakthrough was followed by other ARV drug classes and representatives. Presently, HIV treatment employs 27 ARV representatives belonging to five different classes. Despite the proven benefits of ARV treatment and its long-term control of the HIV infection, there is an increasing concern about the numerous adverse effects and resistance to current ARV drugs. Therefore, the new HIV treatment strategies focus on the development of new ARV agents with a high genetic barrier to resistance and low toxicity. Monoclonal antibodies (MAbs) belong to a new drug class with encouraging results in the treatment of cancer, autoimmune disorders and most recently against HIV infection. The advantages of using MAbs for HIV treatment are related to their antiviral effect, lack of toxicity, good resistance profile, additional synergy with other ARV drug classes and ability to restore CD4 T-cell responses. The current article is a short summary of ibalizumab, an anti-CD4 monoclonal antibody that interferes with HIV viral entry. Current studies on ibalizumab have underlined its antiviral potential, minimal adverse effects, and lack of crossed resistance with other ARV agents thus supporting its further therapeutic use in multidrug resistant HIV-infected patients.

Antibacterial function of the human cathelicidin-18 peptide (LL-37) between theory and practice.

The human cathelicidin-18 is an antimicrobial, immunomodulatory and tissue repair peptide. The LL-37 fragment of this peptide which is in fact the active domain of the cathelicidin-18 is critical for the human antibacterial defense and epithelial integrity. It's activity against resistant pathogens, the potential of epithelial healing after microbial injury and the neutralization of bacterial endotoxin underlie the most important benefits of this peptide. However, there are still a number of questions that remain to be answered regarding the precise interactions of cathelicidin-18 within the immune system, the exact tissue concentrations or its possible pro-tumoral activity. In this respect, the therapeutic potential of cathelicidin-18 in various infections has been proved by in vitro experiments, but additional detailed clinical studies are still required to ascertain its antimicrobial role in vivo. We present a short review on the antibacterial activity of human cathelicidin-18 (LL-37) according to in vitro experiments while discussing its potential use in the clinical practice.

A case of irreversible leukoencephalopathy in a patient with C virus hepatitis treated with pegylated interferon-alpha-2b and ribavirin.

We describe the case of a patient with C chronic hepatitis and early virological response on pegylated-interferon-alpha based therapy who presented clinical manifestations and magnetic resonance imaging suggestive for toxic leukoencephalopathy after 5 months of treatment. The negative results for neurotropic infectious agents and autoimmune markers opened the discussion of toxic interferon-induced leukoencephalopathy as a rare, but threatening neurologic side effect of this therapy.

[Prophylactic antibiotics in neurosurgery]. / Profilaxia cu antibiotice în neurochirurgie.

Because of a low risk of infection (around 2-3%), prophylactic use of antibiotics in neurosurgery is a controversial issue. Some neurosurgeons consider that there are strong arguments against the use of antimicrobials (promotion of antibiotic-resistant strains of bacteria, superinfection and adverse drug reactions) and meticulous aseptic techniques could be more usefully than prophylactic antibiotics. On the other hand, despite of being rare, the consequences of a neurosurgical infection can be dramatic and may result in a rapid death, caused by meningitis, cerebritis, abscess formation or sepsis. Clinical studies emphasized that the most important factors influencing the choice of antibiotic prophylaxis in neurosurgery is the patient's immune status, virulence of the pathogens and the type of surgery ("clean contaminated"--procedure that crosses the cranial sinuses, "clean non-implant"--procedure that does not cross the cranial sinuses, CSF shunt surgery, skull fracture). Prophylaxis has become the standard of care for contaminated and clean-contaminated surgery, also for surgery involving insertion of artificial devices. The antibiotic (first/second generation of cephalosporins or vancomycin in allergic patients) should recover only the cutaneous possibly contaminating flora (S. aureus, S. epidermidis) and should be administrated 30' before the surgical incision, intravenously in a single dose. Most studies pointed that identification of the risk factors for infections, correct asepsis and minimal prophylactic antibiotic regimen, help neurosurgeons to improve patient care and to decrease mortality without selecting resistant bacteria.

Investigation of TNF-alpha, IL-6, IL-8 and of procalcitonin in patients with neurologic complications in sepsis.

Some mediators of inflammation are associated with sepsis, involving nervous system. Proinflammatory cytokines, TNF-alpha, IL-6, and IL-8, and procalcitonin (PCT), proinflammatory protein, were investigated in patients with neurologic complications in sepsis. TNF-alpha, IL-6, IL-8, and PCT were prospectively investigated in 62 patients with neurologic complications in sepsis. TNF-alpha and IL-6 were studied both in serum as in the CSF, IL-8 and PCT were studied only in serum. TNF-alpha, IL-6, and IL-8 were studied by ELISA (R & D Systems), and the PCT by immunoluminometric assay (BRAHMS). Mean value of TNF-alpha in serum was 578+/-214 pg/ml, and in CSF was 458+/-167 pg/ml (p<0.01). Mean value of IL-6 in serum was 749+/-213 pg/ml, and in CSF was 617.5+/-182 pg/ml (p<0.01). Mean value of IL-8 in serum was 332+/-196 pg/ml (p<0.01). Mean value of PCT in serum was 80+/-16 ng/ml (p<0.01). The investigated parameters do not permit the identifying of cases with neurologic complications. The increased correlation coefficient between cytokines in serum and in CSF suggests the damage of the blood-brain barrier. The raise of PCT in serum, induced by TNF-alpha and IL-6, is an argument of the severity of sepsis.