Persistent sepsis-induced transcriptomic signatures in signaling pathways of peripheral blood leukocytes: A pilot study.

Sepsis is a dysregulated immune response to infections that frequently precipitates multiple organ dysfunction and death despite intensive supportive therapy. The aim of the present study was to identify sepsis-induced alterations in the signaling transcriptome of peripheral blood leukocytes that might shed light on the elusive transition from proinflammatory to anti-inflammatory responses and underlie long-term post-sepsis immunosuppression. Peripheral blood leukocytes were collected from subjects (i) with systemic inflammation, (ii) with sepsis in the acute phase and (iii) 6 months after recovery from sepsis, corresponding to progressive stages of the disease. Transcriptomic analysis was performed with the QuantStudio 12K Flex OpenArray Human Signal Transduction Panel analyzing transcripts of 573 genes playing a significant role in signaling. Of them, 145 genes exhibited differential expression in sepsis as compared to systemic inflammation. Pathway analysis revealed enhanced expression levels of genes involved in primary immune responses (proinflammatory cytokines, neutrophil and macrophage activation markers) and signatures characteristic of immunosuppression (increased expression of anti-inflammatory cytokines and proapoptotic genes; diminished expression of T and B cell receptor dependent activating and survival pathways). Importantly, sepsis-induced expression patterns of 39 genes were not normalized by the end of the 6-month follow-up period, indicating expression aberrations persisting long after clinical recovery. Functional analysis of these transcripts revealed downregulation of the antiapoptotic Wnt and mTOR signaling pathways that might explain the post-sepsis immunosuppression commonly seen in sepsis survivors.

Missense Variants of von Willebrand Factor in the Background of COVID-19 Associated Coagulopathy.

COVID-19 associated coagulopathy (CAC), characterized by endothelial dysfunction and hypercoagulability, evokes pulmonary immunothrombosis in advanced COVID-19 cases. Elevated von Willebrand factor (vWF) levels and reduced activities of the ADAMTS13 protease are common in CAC. Here, we aimed to determine whether common genetic variants of these proteins might be associated with COVID-19 severity and hemostatic parameters. A set of single nucleotide polymorphisms (SNPs) in the vWF (rs216311, rs216321, rs1063856, rs1800378, rs1800383) and ADAMTS13 genes (rs2301612, rs28729234, rs34024143) were genotyped in 72 COVID-19 patients. Cross-sectional cohort analysis revealed no association of any polymorphism with disease severity. On the other hand, analysis of variance (ANOVA) uncovered associations with the following clinical parameters: (1) the rs216311 T allele with enhanced INR (international normalized ratio); (2) the rs1800383 C allele with elevated fibrinogen levels; and (3) the rs1063856 C allele with increased red blood cell count, hemoglobin, and creatinine levels. No association could be observed between the phenotypic data and the polymorphisms in the ADAMTS13 gene. Importantly, in silico protein conformational analysis predicted that these missense variants would display global conformational alterations, which might affect the stability and plasma levels of vWF. Our results imply that missense vWF variants might modulate the thrombotic risk in COVID-19.

The results of the first 100 minimal invasive lobectomy in our department / Az elso száz minimálisan invazív tüdolebeny-eltávolítás eredményei osztályunk beteganyagában

Patients and methods: Between 1st November 2013 and 30th June 2019 we performed 112 VATS lobectomies with isolated intubation and anterior approach. In 98 cases lobectomies were performed for malignant lesions, while in 9 cases for benign changes. 78 men and 34 women were operated on. The average age was 60.5 years (42­63). In 5 cases the left upper lobes were resected, in cases 36 the left lower lobes, in 15 cases the right upper lobes, in 11 cases the mid lobes, in 44 cases the right lower lobes, and in one case pneumonectomy was performed. Results: there was no postoperative mortality. Conversion was required in three 3 patients. The average time of surgery was 150 minutes (70­215). Re-operation was needed in two cases due to bleeding and air leakage. Out of the 112 operations, primary lung cancer was demonstrated on pathology in 88 cases, while benign lesions /inflammation in 9 cases. The stages of primary lung cancer were the following: I.a:57, I.b:22, II.a:6, II.b:3 patients. Tumour subtypes were the detailed as 52 adenocarcinoma, 23 squamous cell cc., 2 small cell cc., 5 large cell cc., and 6 carcinoid. 10 patients underwent VATS lobectomy for metastatic disease. Conclusion: As a result of an adequate learning period, VATS lobectomies have become a routine surgery in our unit. Currently 65% of the thoracotomies and more than 50 percent of the lobectomies are performed by the VATS method. Our results are comparable to national as well as international data.

[Necrotizing fasciitis in head and neck area]. / Nekrotizáló fasciitis a fej-nyaki régióban.

Necrotizing fasciitis is a fulminant infection of the deeper layers of skin and subcutaneous tissues characterized by progressive soft tissue necrosis and high mortality. It rarely occurs in the head and neck area. The clinical picture includes non-specific but typical local and systemic symptoms. The treatment is a complex, multidisciplinary task which includes radical surgical exploration, debridement and drainage, empirically started and then targeted intravenous antibiotics and supportive therapy. Authors report a case of necrotizing fasciitis localized on the right side of the face which caused multi-organ failure and phlegmone of the neck.

Assessment of severity and time course of critical illness neuropathy in septic patients: a prospective observational study.

OBJECTIVE: In this prospective observational study we investigated electrophysiological alterations in the early phase of critical illness and correlated electrophysiological findings with the clinical picture and outcome. METHODS: We enrolled 21 critically ill surgical patients having ≥ 12 Acute Physiology and Chronic Health Evaluation (APACHE) II scores on admission. Routine non-invasive bilateral electroneurography (ENG) examination of median and ulnar nerves was done on five consecutive days starting in two days after admission. Then weekly follow-up was performed. Motor and sensory nerve conduction indices were calculated and correlated with APACHE II and Simplified Acute Physiology Score II severity scores. RESULTS: On the first examination 18/21 patients had > 20% reduction in the motor and sensory nerve conduction indices. Severity score systems showed significant negative correlation with the daily change of CMAP and SNAP amplitudes and calculated nerve conduction indices (Spearman's correlation, p < 0.001). Mortality was higher in the patients with worse admission ENG and/or stagnant electrophysiological status or declining tendency in the first week. CONCLUSIONS: Electrophysiological alterations appeared soon after the development of critical illness. Early phase alterations showed a strong correlation with patients' general condition and more severe electrophysiological alterations predisposed to higher mortality. In several cases early alterations proved to be reversible.

Critical illness associated neuromuscular disorders -- keep them in mind.

Neuromuscular disorders complicating sepsis and critical illness are not new and scarce phenomena yet they receive little attention in daily clinical practice. Critical illness polyneuropathy and myopathy affect nearly half of the patients with sepsis. The difficult weaning from the ventilator, the prolonged intensive care unit and hospital stay, the larger complication and mortality rate these disorders predispose to, put a large burden on the patient and the health care system. The aim of this review is to give an insight into the pathophysiological background, diagnostic possibilities and potential preventive and therapeutic measures in connection with these disorders to draw attention to their significance and underline the importance of preventive approach.

Cerebral vasoreactivity to acetazolamide is not impaired in patients with severe sepsis.

INTRODUCTION: The pathophysiology of sepsis-associated encephalopathy (SAE) is not entirely clear, but one of the possible underlying mechanisms is the alteration of the cerebral microvascular function. The aim of the present work was to test whether cerebral vasomotor reactivity is impaired in patients with severe sepsis. METHODS: Patients fulfilling the criteria of clinical sepsis and showing at least 2 organ dysfunctions were included (n = 16). Nonseptic healthy persons without previous diseases affecting cerebral vasoreactivity served as controls (n = 16). Transcranial Doppler blood flow velocities were measured at rest and at 5, 10, 15, and 20 minutes after intravenous administration of 15 mg/kg acetazolamide. The time course of the acetazolamide effect on cerebral blood flow velocity (cerebrovascular reactivity [CVR]) and the maximal vasodilatory effect of acetazolemide (cerebrovascular reserve capacity [CRC]) were compared among the groups. RESULTS: Absolute blood flow velocities after administration of the vasodilator drug did not differ between control and septic patients. Assessment of the time course of the vasomotor reaction showed that patients with sepsis reacted in a similar fashion to the vasodilatory stimulus than control persons. When assessing the maximal vasodilatory ability of the cerebral arterioles to acetazolamide during vasomotor testing, we found that there was no difference in vasodilatory ability between septic and healthy subjects (CRC controls, 54.8% ± 11.1%; CRC sepsis-associated encephalopathy, 61.1% ± 34.4%; P = .49). CONCLUSIONS: We conclude that cerebrovascular reactivity is not impaired in patients with severe sepsis. It is conceivable that cerebral vasoreactivity may be differently involved at different severity stages of the septic process.

[New influenza virus (H1N1) related pneumonia with fatal outcome]. / Az új influenzavírus- (H1N1-) fertozés okozta fatális kimenetelu tüdogyulladás.

The most serious complication of novel influenza virus (H1N1) infections is the progressive respiratory insufficiency caused by diffuse alveolar damage (DAD) which can be overinfected by opportunistic pathogens. Clinically manifest acute respiratory distress syndrome leads to death in the most severe forms of the disease. However, despite the H1N1 positivity determined by RT-PCR, signs of virus pneumonia could not be demonstrated in several cases belonging to the high-risk patient group, therefore, the role of the virus infection in the course of the disease remained unclear. In this paper, a case with a complicated, partially organized hemorrhagic pneumonia and DAD is presented in a patient with H1N1 virus positivity, which can be referred as a classical pulmonary change. In order to obtain correct statistical data on virus related mortality, only unambiguous cases with clear virus associated morphological changes should be considered.