The role of glutamine supplementation in thoracic and upper aerodigestive malignancies.

In cancer patients, marked glutamine (gln) depletion develops over time. Host tissues (epithelial cells and lymphocytes) that depend upon adequate stores of gln for optimal functioning can be negatively influenced. In addition, radiation and/or chemotherapy cause normal tissues damage that might be enhanced by this depletion effect. The present review evaluates in vivo clinical data about the potential beneficial role of gln administration in the prevention of host tissue toxicity, in a patient group with thoracic and upper aerodigestive malignancies (T&UAM) during cancer treatment. Publications were identified in a systematic review of MEDLINE Database from the last 2 decades (1994-2014) using key search terms and through manual searches. Overall, 13 clinical studies (9 oral/4 parenteral) evaluated the safety and tolerance of gln supply, showing a beneficial effect in the grade, duration of mucositis and esophagitis, decreased gut permeability, and weight loss. Only 1 Phase 1 clinical trial had negative results because the chemo-radiotherapy combined treatment was not feasible. The use of oral gln may especially have an important role in the prevention of acute radiation toxicities, the weight loss and the need for analgesics in patients with T&UAM, especially if the treatment plan includes combined modality therapy with chemo-radiation.

COVID-19 and Respiratory Virus Co-Infections: A Systematic Review of the Literature.

Τhe COVID-19 pandemic highly impacted the circulation, seasonality, and morbidity burden of several respiratory viruses. We reviewed published cases of SARS-CoV-2 and respiratory virus co-infections as of 12 April 2022. SARS-CoV-2 and influenza co-infections were reported almost exclusively during the first pandemic wave. It is possible that the overall incidence of SARS-CoV-2 co-infections is higher because of the paucity of co-testing for respiratory viruses during the first pandemic waves when mild cases might have been missed. Animal models indicate severe lung pathology and high fatality; nevertheless, the available literature is largely inconclusive regarding the clinical course and prognosis of co-infected patients. Animal models also indicate the importance of considering the sequence timing of each respiratory virus infection; however, there is no such information in reported human cases. Given the differences between 2020 and 2023 in terms of epidemiology and availability of vaccines and specific treatment against COVID-19, it is rational not to extrapolate these early findings to present times. It is expected that the characteristics of SARS-CoV-2 and respiratory virus co-infections will evolve in the upcoming seasons. Multiplex real-time PCR-based assays have been developed in the past two years and should be used to increase diagnostic and infection control capacity, and also for surveillance purposes. Given that COVID-19 and influenza share the same high-risk groups, it is essential that the latter get vaccinated against both viruses. Further studies are needed to elucidate how SARS-CoV-2 and respiratory virus co-infections will be shaped in the upcoming years, in terms of impact and prognosis.

Carbapenem-Resistant Pseudomonas aeruginosa Bacteremia, through a Six-Year Infection Control Program in a Hospital.

BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is a life-threatening healthcare-associated infection affecting especially patients with immunosuppression and comorbidities. We investigated the association between the incidence of CRPA bacteremia, antibiotic consumption, and infection control measures in a hospital during 2013-2018. METHODS: We prospectively recorded the incidence of CRPA bacteremia, antibiotic consumption, use of hand-hygiene solutions, and isolation rates of multidrug-resistant (MDR) carrier patients. FINDINGS: The consumption of colistin, aminoglycosides, and third-generation cephalosporins decreased significantly in the total hospital and its divisions (p-value < 0.001 for all comparisons) while the consumption of carbapenems decreased significantly in the adults ICU (p-value = 0.025). In addition, the incidence of CRPA significantly decreased in the total hospital clinics and departments (p-values = 0.027 and 0.042, respectively) and in adults clinics and departments (p-values = 0.031 and 0.051, respectively), while in the adults ICU, the incidence remained unchanged. Increased isolation rates of MDR carrier patients, even two months before, significantly correlated with decreased incidence of CRPA bacteremia (IRR: 0.20, 95% CI: 0.05-0.73, p-value = 0.015) in the adults ICU. Interestingly, when the use of hand-hygiene solutions (alcohol and/or scrub) increased, the consumption of advanced, nonadvanced, and all antibiotics decreased significantly. CONCLUSION: In our hospital, multimodal infection control interventions resulted in a significant reduction of CRPA bacteremia, mostly due to the reduction of all classes of antibiotics.

The Burden of COVID-19 in Adult Patients With Hematological Malignancies: A Single-center Experience After the Implementation of Mass-vaccination Programs Against SARS-CoV-2.

BACKGROUND/AIM: Despite the widespread mass-vaccination programs worldwide and the continuing evolution of COVID-19 therapeutics, the burden of SARS-CoV-2 infection in patients with hematological malignancies (HM) remains elusive. The aim of the present study was to assess the clinical characteristics, outcomes and therapeutic strategies applied in HM patients hospitalized during the post-vaccine period in Greece. PATIENTS AND METHODS: From June 2021 to October 2022, 60 HM patients with COVID-19 were retrospectively analyzed. Exploratory end-points included the incidence of intubation, probability of recovery, mortality, and duration of remdesivir (RDV) administration. RESULTS: Overall, mechanical ventilation (MV) was required for five patients and crude mortality was 8.3%. HM of lymphocytic origin (p=0.035) and obesity (p=0.03) were the main determinants of the risk of intubation and among several laboratory markers, only LDH>520 IU/l was proven to be an independent MV predictor (p=0.038). The number of co-existing comorbidities (p=0.05) and disease severity on admission (p<0.001) were found to rule the probability of recovery, and dexamethasone was associated with worse prognosis, particularly in patients with mild/moderate COVID-19. RDV was administered to the entire cohort, of whom 38 were managed with an extended course. In the multivariate analysis, patients with HM of lymphocytic origin were more likely to receive RDV for more than five days (p=0.002). CONCLUSION: Our study emphasizes the frailty of HM patients, even in the era of Omicron-variant predominance, and underlines the need to optimize therapy.

Prolonged SARS-CoV-2 Infection With Common Features in Two Patients Receiving Anti-CD20 Therapy.

BACKGROUND/AIM: Anti-CD20-depleting monoclonal antibodies predispose patients to the development of severe disease of SARS-CoV-2 infection. These antibodies are given as backbone or maintenance therapy in patients with hematological malignancies and rheumatology diseases, inducing effective B-cell depletion along with antibody-dependent cell-mediated cytotoxicity (ADCC) and disrupting infection-protective antibody responses. CASE REPORT: We describe two cases of prolonged SARS-CoV-2 infection with common features, in two patients receiving anti-CD20 therapies, the first for chronic lymphocytic leukemia (CLL) and the second for rheumatoid arthritis (RA). For CLL patient, despite administration of antiviral therapy, signs and symptoms of SARS-CoV-2 infection persisted for 43 days, with resolution and lymphocyte recovery from day 33. For RA patient, despite administration of two courses of antiviral therapy, signs and symptoms of SARS-CoV-2 infection persisted for 47 days, without resolution and lymphocyte recovery, leading to a fatal outcome due to acute respiratory distress syndrome (ARDS) and unspecified sepsis. CONCLUSION: These two cases highlight the risk for persistent SARS-CoV-2 infection in patients treated with anti-CD20 monoclonal antibodies and support a role for cellular immunity recovery for disease control.

Association between consumption of antibiotics, infection control interventions and Clostridioides difficile infections: Analysis of six-year time-series data in a tertiary-care hospital in Greece.

BACKGROUND: To investigate the association between Clostridioides difficile infection (CDI), antibiotic use, and infection control interventions, during an antibiotic stewardship program (ASP) implemented in a tertiary-care hospital in Greece from 2013 to 2018. METHODS: Analysis was applied for the following monthly indices: 1. consumption of antibiotics; 2. use of hand hygiene disinfectant solutions; 3. percentage of isolations of patients either with multidrug-resistant (MDR) bacteria, or CDI, or admitted from another hospital; and 4. percentage of patients with CDI divided into two groups: community-acquired CDI (CACDI) and hospital-associated CDI (HACDI) (onset ≤72 h and >72 h after admission, respectively). RESULTS: During the study, a significant reduction in CACDI rate from 0.3%/admissions [95% CI 0.1-0.6] to 0.1%/admissions [95% CI 0.0-0.3] (p-value = 0.035) was observed in adults ICU, while CDI rates were stable in the rest of the hospital. Antibiotic consumption showed a significant reduction in total hospital, from 91.7 DDDs [95% CI 89.7-93.7] to 80.1 DDDs [95% CI 79.1-81.1] (p-value<0.001), except adults ICU. Non-advanced antibiotics correlated with decreased CDI rates in Adults Clinic Departments and ICU. Isolation of patients one and two months earlier correlated with decreased CACDI rates per 20% [95% CI 0.64-1.00, p-value = 0.046] and HACDI per 23% [95% CI 0.60-1.00, p-value = 0.050] in Adults Clinic Departments. Consumption of disinfectant solutions current month correlated with decreased rate for CACDI per 33% [95% CI 0.49-0.91, p-value = 0.011] and HACDI per 38% [95% CI 0.40-0.98, p-value = 0.040] in total Hospital Clinics. CONCLUSION: Rational antibiotic prescribing during ASP along with multipronged intervention strategy focusing on hand hygiene and patient isolation measures prevent and control CDI outbreaks in the hospital setting.

Use of oral glutamine in radiation-induced adverse effects in patients with thoracic and upper aerodigestive malignancies: Results of a prospective observational study.

Cancer growth in host tissues features glutamine (gln) depletion over time, decreasing epithelial cells' optimal functioning. In addition, radiotherapy (RT) and/or chemotherapy (CT) cause damage to normal tissues, probably enhanced by this depletion. The present study prospectively examined the effect of gln supplementation on 72 patients with thoracic and upper aerodigestive malignancies (T&UAM) treated with sequential or concurrent RT-CT or RT alone. All patients received prophylactic gln powder 15 g bid for the full duration of treatment. The severity of acute radiation toxicities was graded according to the RT Oncology Group/European Organization for Research and Treatment of Cancer criteria. Primary endpoints were the incidence of grade >2 toxicities, weight loss and requirement for analgesics, and the secondary endpoint was the association of the length of irradiated esophagus from treatment planning with the use of opioids. The incidence of adverse effects was as follows: Grade >2 stomatitis, 25.0%; esophagitis, 60.5%; dysphagia, 54.2%; pain, 25.4%; mycosis, 40.8%. Stomatitis grade >2 was more frequent in patients with head and neck tumors (P<0.001) and in those with prior surgery (P<0.001). Esophagitis (P=0.020) and dysphagia (P=0.008) grade >2 were more frequent in patients with concurrent RT-CT. Regarding analgesics, 9.9% of patients received no pain treatment, 56.3% received simple analgesic therapy and 33.8% opioids. Patients on opioid therapy had a greater mean length of irradiated esophagus (P=0.024) or length >12 cm (P=0.018). In 54.2% of patients, weight loss was observed, particularly with concurrent RT-CT (P=0.007). Thus, the use of oral gln may have an important role in reducing acute radiation toxicities and weight loss, and in lowering the requirement for analgesics in patients with T&UAM. Further randomized trials are required to identify the appropriate gln dose, duration of treatment and precise radiation dosimetric parameters in this group of patients. The present clinical trial was retrospectively registered in the ClinicalTrials.gov Protocol Registration and Results System (registration no. NCT05054517/22-09-2021).

Six-Year Time-Series Data on Multidrug-Resistant Bacteremia, Antibiotic Consumption, and Infection Control Interventions in a Hospital.

Background: Multidrug-resistant (MDR) bacteremia is a serious health care-associated infection with significant morbidity and excess hospitalization costs. Our aim is to study the association between incidences of MDR bacteremia, antibiotic consumption, and infection control measures in a hospital from 2013 to 2018. Methods: We analyzed the following indices: (1) incidence of bacteremia (carbapenem-resistant Acinetobacter baumanii, Pseudomonas aeruginosa, and Klebsiella pneumoniae, methicillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococci); (2) use of antibiotics; (3) consumption of disinfectant solutions for hand hygiene; and (4) isolation rates of MDR carrier patients. Findings: The use of advanced antibiotics (p = 0.001) and carbapenems (p = 0.008) decreased significantly in all hospital departments but the incidence of total MDR bacteremia did not change significantly. Increased use of hand disinfectant solutions was statistically associated with decreased incidence of total MDR bacteremia (incidence rate ratio [IRR]: 0.94, confidence interval [95% CI]: 0.90-0.99, p: 0.020) in all hospital. Also, increased isolation rates of MDR carrier patients 2 months before correlated with decreased incidence of bacteremia due to carbapenem-resistant gram-negative pathogens (IRR: 0.35, 95% CI: 0.18-0.66, p: 0.001) in adults intensive care unit. Conclusion: In our hospital, hand hygiene and isolation of MDR carrier patients controlled MDR bacteremia.

Ventilator-Associated Pneumonia, Multidrug-Resistant Bacteremia and Infection Control Interventions in an Intensive Care Unit: Analysis of Six-Year Time-Series Data.

Ventilator-associated pneumonia (VAP) occurs more than 48h after mechanical ventilation and is associated with a high mortality rate. The current hospital-based study aims to investigate the association between VAP rate, incidence of bacteremia from multidrug-resistant (MDR) pathogens, and infection control interventions in a single case mix ICU from 2013 to 2018. Methods: The following monthly indices were analyzed: (1) VAP rate; (2) use of hand hygiene disinfectants; (3) isolation rate of patients with MDR bacteria; and (4) incidence of bacteremia/1000 patient-days (total cases, total carbapenem-resistant cases, and carbapenem-resistant Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae cases separately). Results: Time trends of infection control interventions showed increased rates in isolation of patients with MDR pathogens (p <0.001) and consumption of hand disinfectant solutions (p =0.001). The last four years of the study an annual decrease of VAP rate by 35.12% (95% CI: −53.52 to −9.41; p =0.01) was recorded, which significantly correlated not only with reduced trauma and cardiothoracic surgery patients (IRR:2.49; 95% CI: 2.09−2.96; p <0.001), but also with increased isolation rate of patients with MDR pathogens (IRR: 0.52; 95% CI: 0.27−0.99; p = 0.048), and hand disinfectants use (IRR: 0.40; 95% CI: 0.18−0.89; p =0.024). Conclusions: Infection control interventions significantly contributed to the decrease of VAP rate. Constant infection control stewardship has a stable time-effect and guides evidence-based decisions.

Catheter-Associated Urinary Tract Infections, Bacteremia, and Infection Control Interventions in a Hospital: A Six-Year Time-Series Study.

Catheter-associated urinary tract infections (CAUTIs) are among the most common healthcare-associated infections. Urine catheters are often reservoirs of multidrug-resistant (MDR) bacteria and sources of pathogens transmission to other patients. The current study was conducted to investigate the correlation between CAUTIs, MDR bacteremia, and infection control interventions, in a tertiary-care hospital in Athens, from 2013 to 2018. The following data were analyzed per month: 1. CAUTI incidence; 2. consumption of hand hygiene disinfectants; 3. incidence of isolation of MDR carrier patients, and 4.incidence of bacteremia/1000 patient-days [total resistant a.Gram-negative: carbapenem-resistant Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae; b.Gram-positive: vancomycin-resistant Enterococci and methicillin-resistant Staphylococcus aureus]. The use of scrub disinfectant solutions was associated with decreased CAUTI rate in Total Hospital Clinics (OR: 0.97, 95% CI: 0.96−0.98, p-value: <0.001) and in Adults ICU (OR: 0.79, 95% CI: 0.65−0.96, p-value:0.018) while no correlation was found with isolation rate of MDR-carrier pathogens. Interestingly, an increase in total bacteremia (OR: 0.81, 95% CI: 0.75−0.87, p-value:<0.001) or carbapenem-resistant bacteremia correlated with decreased incidence of CAUTIs (OR: 0.96, 95% CI: 0.94−0.99, p-value: 0.008). Hand hygiene measures had a robust and constant effect on infection control, reducing the incidence of CAUTIs.

The multi-cancer marker, rs6983267, located at region 3 of chromosome 8q24, is associated with prostate cancer in Greek patients but does not contribute to the aggressiveness of the disease.

BACKGROUND: Recently, several polymorphisms located on human chromosome 8q24 were found to be associated with prostate cancer risk with different frequency and incidence among the investigated populations. The authors conducted a prostate cancer case-control study in the Greek population to evaluate the association of the single nucleotide polymorphism (SNP) rs6983267, located at region 3 of chromosome 8q24, with this type of cancer. METHODS: Samples of total blood from 86 patients with histologically confirmed prostate cancer and 99 healthy individuals were genotyped using real time polymerase chain reaction (PCR). Tumor-node-metastasis (TNM) stage, Gleason score and levels of prostate-specific antigen (PSA) at diagnosis were included in the analysis. RESULTS: A highly significant association (odds ratio=2.84 and p-value=0.002) was found between rs6983267 and prostate cancer in the Greek population. The sensitivity, specificity, negative and positive predictive values of the presence of G allele for the discrimination between patients and controls were 81.40%, 39.4%, 53.9% and 70.9%, respectively. A lower proportion of homozygotes was found in patients with PSA level <4 ng/mL compared to those with PSA level more than 4 ng/mL (p=0.019). None of the other clinical factors nor the aggressiveness of the disease were found to be significantly associated with rs6983267 genotype. CONCLUSIONS: The SNP rs6983267 is an established marker for a range of cancers. In prostate cancer, it indicates an enhanced risk for carriers to develop the disease in general. In our study it showed no association with aggressive forms or familial and early-onset prostate cancer families.