Trends in Molecular Diagnosis of Nosocomial Pneumonia Classic PCR vs. Point-of-Care PCR: A Narrative Review.

Nosocomial pneumonia is one of the most frequent hospital-acquired infections. One of the types of nosocomial pneumonia is ventilator-associated pneumonia, which occurs in endotracheally intubated patients in intensive care units (ICU). Ventilator-associated pneumonia may be caused by multidrug-resistant pathogens, which increase the risk of complications due to the difficulty in treating them. Pneumonia is a respiratory disease that requires targeted antimicrobial treatment initiated as early as possible to have a good outcome. For the therapy to be as specific and started sooner, diagnostic methods have evolved rapidly, becoming quicker and simpler to perform. Polymerase chain reaction (PCR) is a rapid diagnostic technique with numerous advantages compared to classic plate culture-based techniques. Researchers continue to improve diagnostic methods; thus, the newest types of PCR can be performed at the bedside, in the ICU, so-called point of care testing-PCR (POC-PCR). The purpose of this review is to highlight the benefits and drawbacks of PCR-based techniques in managing nosocomial pneumonia.

Effects of Tocilizumab on Inflammation and Iron Metabolism in Critically Ill Patients with COVID-19.

COVID-19 produces cytokine-mediated persistent inflammation and is associated with elevated iron stores and low circulating iron. It is believed that central to the pathophysiological mechanism is interleukin 6 and hepcidin. A state of iron overload, termed hyperferritinemia, and inflammatory anemia take place. Both conditions are linked to a worse result in critically ill patients. Blocking the interleukin 6-hepcidin pathway with Tocilizumab could present favorable outcomes. The aim of this study was to evaluate if Tocilizumab influences survival, the occurrence of sepsis, anemia and transfusions in critically ill patients suffering from COVID-19. This prospective observational study focused on levels of interleukin 6, hepcidin and blood iron parameters in patients treated with Tocilizumab. Data were compared before and after therapy as well as between treated and control groups. Results indicate that there is no difference in terms of survival nor in the rate of anemia or sepsis occurrence. Hepcidin was elevated and anemia ensued after treatment, which could indicate alternative pathways. In conclusion, when the classic interleukin 6-hepcidin pathway is blocked, inflammation seems to use alternative routes. Further understanding of these pathways is required and new pharmacological therapies need to be developed to treat persistent inflammation.

Hyperferritinemia, Low Circulating Iron and Elevated Hepcidin May Negatively Impact Outcome in COVID-19 Patients: A Pilot Study.

Inflammation in COVID-19 produces intracellular iron overload with low circulating iron available for metabolic processes. The accumulated intracellular iron generates reactive species of oxygen and results in ferroptosis, a non-programmed cell death. Since no organ is spared, iron dysmetabolism increases the mortality and morbidity. Hepcidin and the mediator interleukin 6 are believed to play a role in the process. Our aim is to evaluate the predictive values of serologic iron and inflammatory parameters in COVID-19 critically ill patients. Hence, 24 patients were included. Hepcidin and interleukin 6, along with routine blood parameters, were determined and outcomes, such as death, multiple organ damage (MOD), anemia, and need for transfusions, were assessed. The results of this pilot study indicate that iron metabolism parameters individually, as well as models consisting of multiple laboratory and clinical variables, may predict the outcomes. Further larger studies are needed to validate the results of this pilot stud. However, this paper identifies a new direction for research.

The Role of Circulating Tumor Cells in the Prognosis of Metastatic Triple-Negative Breast Cancers: A Systematic Review of the Literature.

Breast cancer is one of the leading causes of death in women worldwide. One subtype of breast cancer is the triple-negative, which accounts for 15% of total breast cancer cases and is known for its poor prognosis. The main cause of death is due to metastasis. Circulating tumor cells (CTCs) play a key role in the metastatic process. CTCs arise either by detaching from the primary tumor or from cancer stem cells undergoing an epithelial-to-mesenchymal transition (EMT). This review aims to present up-to-date data concerning the role of CTC numbers in relation to the prognostic and treatment response in metastatic triple-negative breast cancer (mTNBC) patients, and also to discuss the methods used for CTCs' identification. A search in the MEDLINE database was performed. A total of 234 articles were identified. The results of the 24 eligible studies showed that positive CTC status is associated with shorter overall survival (OS) and progression-free survival (PFS) in mTNBC patients. Furthermore, a decrease in number of CTCs during therapy seems to be a favorable prognostic factor, making CTCs' detection an important prognostic tool before and during therapy in mTNBC patients. The methods used for CTC detection are still developing and need further improvement.

The Significance of Duration of Exposure and Circulation of Fresh Air in SARS-CoV-2 Transmission Among Healthcare Workers.

Background: The true risk of infection after exposure to SARS-CoV-2 of healthcare workers (HCWs) in the workplace has not yet been established. This descriptive study analyzes the exposure characteristics of HCWs to SARS-CoV-2. Methods: In March 2020, at the beginning of the pandemic, a total of 58 HCWs in a regional hospital in Greece were exposed to three patients with symptomatic SARS-CoV-2 infection. These three index cases had taken part in an 8-day religious tour, during which 52 travelers spent 10 h every day in a tour bus. A study was made of the circumstances of the hospital exposure. Results: Of the 52 travelers in the bus, 48 contracted SARS-CoV2. None of the 58 HCW contacts developed symptoms related to COVID-19, although, 43% were exposed to a SARS-CoV-2 infected patient for more than 15 min, and 74% were within a distance of <1 m, and half of the contacts were not wearing a surgical mask. Additional information was that 63% of the contacts were exposed in a room sized more than 15 m2, and in more than 80% of cases, the window or the door to the room was open during their exposure. In about one-third of the exposure events, the HCW contacts were not wearing a mask and were at a distance of <1 m, and just under half of them were exposed for more than 15 min. One-fourth of the contacts underwent RT-PCR testing, and 11% IgG/IgM antibody testing for SARS-CoV-2, all of which were negative. All observed quarantine at home for 14 days. Conclusion: This observational study was made before the extent of the SARS-CoV-2 became apparent, and before routine preventive measures were observed by all HCWs. Comparing the conditions of exposure in the two different settings (bus vs. regional health facility), it is apparent that the duration of exposure and the small, enclosed nature of the bus are the distinguishing factors. In the healthcare setting, the elimination of both factors and the implementation of additional measures protected the exposed HCWs from contracting SARS-CoV-2 infection.

Clinical versus Ultrasound Measurements of Hyomental Distance Ratio for the Prediction of Difficult Airway in Patients with and without Morbid Obesity.

PURPOSE: To describe the correlation between clinically measured hyomental distance ratio (HMDRclin) and the ultrasound measurement (HMDRecho) in patients with and without morbid obesity and to compare their diagnostic accuracy for difficult airway prediction. METHODS: HMDRclin and HMDRecho were recorded the day before surgery in 160 consecutive consenting patients. Laryngoscopy was performed by a skilled anesthesiologist, with grades III and IV Cormack-Lehane being considered difficult views of the glottis. Linear regression was used to assess the correlation between HMDRclin and HDMRecho and receiver operating curve analysis was used to compare the performance of the two for predicting difficult airway. RESULTS: The linear correlation between HMDRclin and HDMRecho in patients without morbid obesity had a Pearson coefficient of 0.494, while for patients with morbid obesity this was 0.14. A slightly higher area under the curve for HMDRecho was oberved: 0.64 (5%CI 0.56-0.71) versus 0.52 (95%CI, 0.44-0.60) (p = 0.34). CONCLUSION: The association between HMDRclin and HDMRecho is moderate in patients without morbid obesity, but negligible in morbidly obese patients. These might be explained by difficulties in palpating anatomical structures of the airway.

Periodontal disease might be a risk factor for graft versus host disease. A systematic review.

PURPOSE: The aim of this systematic review was to determine a potential association between periodontal disease and graft versus host disease (GVHD). DESIGN: PubMed, Scopus and Web of Science databases were searched to identify all relevant articles. The eligibility criteria were prospective, retrospective, cross-sectional, cohort, case-control studies and interventional studies that assessed periodontal parameters in GVHD adults' patients. RESULTS: Seven studies, published between 2000 and 2018, were eligible. The aggravation of periodontal tissues is due to inadequate oral hygiene, dental plaque, decays, gum recession, retained roots, tooth loss, periodontally infected teeth. Several studies have indicated that periodontitis treatment performed before transplantation showed the reduction of gingival inflammation and maintenance of periodontal health. CONCLUSIONS: Periodontitis might be a risk factor for GVHD. However, due to the limited number of studies included in the review and their heterogeneity, more data are needed to sustain the correlation between periodontitis and GVHD.

Approach to the Adult Acute Lymphoblastic Leukemia Patient.

During recent decades, understanding of the molecular mechanisms of acute lymphoblastic leukemia (ALL) has improved considerably, resulting in better risk stratification of patients and increased survival rates. Age, white blood cell count (WBC), and specific genetic abnormalities are the most important factors that define risk groups for ALL. State-of-the-art diagnosis of ALL requires cytological and cytogenetical analyses, as well as flow cytometry and high-throughput sequencing assays. An important aspect in the diagnostic characterization of patients with ALL is the identification of the Philadelphia (Ph) chromosome, which warrants the addition of tyrosine kinase inhibitors (TKI) to the chemotherapy backbone. Data that support the benefit of hematopoietic stem cell transplantation (HSCT) in high risk patient subsets or in late relapse patients are still questioned and have yet to be determined conclusive. This article presents the newly published data in ALL workup and treatment, putting it into perspective for the attending physician in hematology and oncology.

Increased Susceptibility to Postoperative PCA Morphine-Induced Respiratory Depression in a Patient with an Undiagnosed Traumatic Porencephalic Cyst - A Case Report.

INTRODUCTION: Patient-controlled analgesia with morphine is routinely used for postoperative pain management. Due to the safety profiles of the technique, which are patient/disease related or technique/equipment related, severe respiratory depression requiring opioid antagonists or airway management are uncommon. CASE PRESENTATION: The case of a patient with right colon carcinoma who was operated on for hemicolectomy under general anaesthesia and who presented with apnoea, after postoperatively receiving an initial bolus of 1mg of morphine. A large post-traumatic porencephalic cyst of the left brain hemisphere, previously undiagnosed, was found on the computed tomography scan. We excluded human errors, technique and equipment factors, and the patient did not have any other predisposing conditions like sleep apnoea, obesity, recent head injury or concurrent use of other sedatives. Previously the patient had been entirely asymptomatic, and her increased susceptibility to respiratory depression was the only clinical manifestation of porencephaly. CONCLUSION: Adult acquired porencephaly is seldom reported in the literature, clinical manifestations depending on the location and size of the cyst. In the present reported case, increased susceptibility to low-dose opioids might be associated with the structural and functional reorganisation of the brain after head trauma with the occurrence of the porencephalic cyst of the brain.

Preoperative difficult airway prediction using suprahyoid and infrahyoid ultrasonography derived measurements in anesthesiology.

Airway management is one of the most important skills in everyday practice of anesthesia. Improper airway management might contribute to significant morbidity and mortality. In some patients, clinical parameters do not anticipate all difficulties related to airway management. Ultrasonography (US) might confer a potential screening tool for difficult airway. Suprahyoid and infrahyoid US measurements have been investigated for difficult airway prediction in anesthesiology. The most extensively investigated parameter was the anterior neck soft tissue thickness measured at different levels: anterior to the hyoid bone, epiglottis and vocal cords commissure. Hyomental distances measured with the head placed in neutral, sniffing or maximal hyperextended position and the derived hyomental distance ratios have also been evaluated for difficult airway prediction. For the evaluation of the tongue, measurements such as thickness, cross-sectional area, width, volume and tongue-to-oral cavityratio can be used. Thus, anesthesiologists have many available potential US measurements, which could provide information regarding airway anatomy during the preoperative airway assessment and could serve as potential screening parameters for difficult airway. Still, we do not yet know which of these provides optimal predictive accuracy and larger sample size studiesare required to validate their use in the preoperative evaluation of the airway.

Correction: Genetically enhanced T lymphocytes and the intensive care unit.

[This corrects the article DOI: 10.18632/oncotarget.24637.].

Genetically enhanced T lymphocytes and the intensive care unit.

Chimeric antigen receptor-modified T cells (CAR-T cells) and donor lymphocyte infusion (DLI) are important protocols in lymphocyte engineering. CAR-T cells have emerged as a new modality for cancer immunotherapy due to their potential efficacy against hematological malignancies. These genetically modified receptors contain an antigen-binding moiety, a hinge region, a transmembrane domain, and an intracellular costimulatory domain resulting in lymphocyte T cell activation subsequent to antigen binding. In present-day medicine, four generations of CAR-T cells are described depending on the intracellular signaling domain number of T cell receptors. DLI represents a form of adoptive therapy used after hematopoietic stem cell transplant for its anti-tumor and anti-infectious properties. This article covers the current status of CAR-T cells and DLI research in the intensive care unit (ICU) patient, including the efficacy, toxicity, side effects and treatment.

Acute poisoning due to ingestion of Datura stramonium - a case report.

Datura stramonium (DS) is a widespread annual plant, containing atropine, hyoscyamine, and scopolamine, which can produce poisoning with a severe anticholinergic syndrome. Teenagers ingest the roots, seeds or the entire plant to obtain its hallucinogenic and euphoric effects. We presented the case of a 22 year old male who was admitted to the Emergency Room in a coma after consuming Datura stramonium, 2 hours earlier. The patient presented with fever, tachycardia with right bundle branch block, and urinary retention. Rapid sequence induction and intubation was performed immediately, with sedation and assisted-control mechanical ventilation, after being transferred to the Intensive Care Unit. The patient received activated charcoal, in repeated doses, external and internal cooling was applied, and an infusion of neostigmine was started. The biological assessment revealed rhabdomyolysis and prevention of renal failure was initiated. After a proper neurological evaluation, 36 hours after using Datura stramonium, the patient was extubated and transferred to the Psychiatric ward for further assessment and care.

Lethal case of Vipera bersus bite.

Adder bites are rare events, but they can be fatal. Three adder types live in Romania - Vipera ammodytes, Vipera ursini and Vipera berus. Most adder bites happen during the summer with a peak incidence between July and August. Here we present the case of a 56 years old male patient who was bitten by an adder. The clinical presentation was severe from the beginning with a GCS of 3 points, respiratory and cardiovascular failure; despite of adequate treatment the patient developed multiorgan dysfunction and died 36 hours after the ICU admission. The aim of this report is to raise awareness that snake bites can have a life-threatening course and need immediate attention and medical care.

Can APACHE II, SOFA, ISS, and RTS Severity Scores be used to Predict Septic Complications in Multiple Trauma Patients?

BACKGROUND: Physiological composite scores are used to predict mortality in multiple trauma patients. Sepsis is the leading cause of late mortality in trauma victims brought about by immune suppression due to homeostasis dysregulation. OBJECTIVE: To determine whether APACHE II, SOFA, ISS and RTS scores can predict the occurrence of sepsis in multiple trauma patients. METHODS: APACHE II, SOFA, ISS, and RTS scores were calculated during the first twenty-four hours after the injury for sixty-four adult poly-traumatic patients. The occurrence of infectious complications was investigated over a fourteen-day period. The infection-free rates for the multiple trauma patients were considered as end-points in the Kaplan-Meier plot analysis. RESULTS: For SOFA, a cutoff score of 4 points was identified as a predictor of the occurrence of sepsis, with 89% of the patients with SOFA<4 being infection-free, while 37% of those with SOFA>4 were infection-free (p<0.01). None of the patients with APACHE II≤5 points developed infections. Eighty-four percent of patients with APACHE II scores of 5-10 did not develop sepsis, while 49% with APACHE II≥11 were infection-free (p<0.01). A cutoff of 7 points was found to be most discriminative for RTS. Eighty-eight percent of the patients with RTS≤7 and 43% of those with RTS<7 were infection-free (p<0.01). Eighty-eight percent of patients with ISS≥22 did not develop sepsis and 56% with ISS>22 did not develop sepsis (p<0.01). CONCLUSION: APACHE II, SOFA, ISS, and RTS functional severity scores can predict mortality as well as the occurrence of sepsis in multiple trauma patients.

Biomarkers in polytrauma induced systemic inflammatory response syndrome and sepsis - a narrative review.

Polytrauma still represents one of the leading causes of death in the first four decades of life. Septic complications represent the predominant causes of late death in polytrauma patients. Early diagnosis and treatment of infection is associated with an improved clinical outcome and reduced mortality. Several biomarkers have been evaluated for making early diagnosis of sepsis. Current evidence does not support the use of a single biomarker in diagnosing septic complications. Procalcitonin trend was found to be useful in early identification of post-traumatic sepsis.

A fatal case of Taxus poisoning.

CONTEXT: Taxine-derived alkaloids, taxane-derived substances, and glycosides seem to be responsible for the toxicity of Taxus spp. by blocking microtubule, sodium and calcium channels causing conduction abnormalities. Cases with Taxus baccata acute intoxication have rarely been reported. CASE DETAILS: We report the case of a 43-year-old man who ingested, for suicidal purposes, common (or European) yew leaves (Taxus baccata) and presented severe hypokalemia, ventricular arrhythmias with hemodynamic instability accompanied by severe multiple organ dysfunction syndrome, including respiratory insufficiency, renal failure, acid-base imbalance with severe hypokalemia, hepatic dysfunction and coma, which led to death 12 hours after Taxus baccata ingestion. CONCLUSION: In this particular case, the cardiac electrical instability was definitely maintained by several causes, including severe hypokalemia, which has not been previously reported as related to Taxus poisoning. The metabolic acidosis associated with severe hypokalemia definitely contributed to the complex arrhythmias. The occurrence of severe hypokalemia needs further attention in cases with Taxus poisoning as its immediate treatment might increase survival chances.

Is a positive history of non-anaesthetic drug allergy a predictive factor for positive allergy tests to anaesthetics?

AIMS: International recommendations stipulate not performing screening skin tests to a drug in the absence of a clinical history consistent with that specific drug allergy. Nevertheless, two publications showed that a positive history of non-anaesthetic drug allergy was the only predictive factor for a positive skin test when screening for allergy to anaesthetic drugs was done. We selected from a surgical population 40 volunteers with a prior history of allergy to non-anaesthetic drugs in order to analyse the prevalence of positive allergy tests to anaesthetics. METHODS: The selected adult patients were tested for 11 anaesthetic drugs using in vivo tests: skin prick (SPT) and intradermal (IDT) tests and in vitro tests: the basophil activation test (BAT) and detection of drug-specific immunoglobulin E (IgE). RESULTS: The prevalence for the positive SPT and IDT was 1.6% and 5.8% respectively. The result of flow cytometry agreed with the SPT in five out of seven positive SPT (71%). IgEs confirmed two positive SPT with corresponding positive BAT. Ten per cent of the patients had a positive prick test to neuromuscular blocking agents (NMBA). For midazolam none of the SPT was positive, but 11 patients had positive IDT nonconfirmed by BAT. CONCLUSION: The prevalence of positive in vivo and in vitro allergy tests to NMBAs is higher in our study population. This could be an argument for pre-operative SPT to NMBAs for the surgical population with reported non-anaesthetic drug allergies. A larger prospective study is needed to validate changes in clinical practice.