Severe community- acquired pneumonia – studies on imaging, etiology, treatment, and outcome among intensive care patients

Abstract Pneumonia is a common diagnosis for intensive care unit (ICU) admission. In 2012, 51% of the ICU-treated infections in Finland were of pulmonary origin. The ICU-treated pneumonias can be classified according to acquisition of infection as community-acquired (CAP) or hospital-acquired (HAP). Ventilator-associated pneumonia (VAP) is a subtype of HAP. Patients with severe community-acquired pneumonia (SCAP) require ICU treatment due to need of mechanical ventilation or hemodynamic support. SCAP is associated with high morbidity and high ICU and hospital mortality. The aim of this observational study was to evaluate the clinical characteristics and outcome of SCAP, with special interest on imaging, viral etiology, combination antibiotic treatment and long-term outcome. The thesis comprises three retrospective studies with altogether 392 SCAP patients, median age 55 years, 55.9% of them male. The usefulness of early chest CT and β-lactam-respiratory quinolone (βQ) versus β-lactam-macrolide (βM) therapy for SCAP treatment was evaluated. The hospital and long-term outcomes of SCAP patients were compared with 66 HAP and 25 VAP cases. A prospective study included 49 mechanically ventilated SCAP patients. The frequency of viral etiology in SCAP was analyzed. In SCAP patients, the chest CT as compared to the chest radiograph yielded new imaging findings for 58.5% of the SCAP patients. This information led to procedures or treatment changes in 43% of the cases. The severity of oxygenation disorder correlated to the extent of lung involvement. In prospective SCAP series ICU- mortality was 6.1% and hospital mortality was 12.2%. Viral etiology was found to be common in SCAP and viruses were demonstrated in 49% of patients. The outcome was similar whether SCAP patients were treated with βQ or βM combination. The type of pneumonia did not have a significant association with hospital mortality in ICU-treated SCAP, HAP and VAP patients. Among the hospital survivors, the long-term mortality was substantial, SCAP patients representing the best 1-year outcome. In conclusion, early CT might be useful in SCAP diagnostics and treatment. Viral etiology is common in SCAP. Both β-lactam-respiratory quinolone and β-lactam macrolide combinations were equally good in SCAP treatment. Hospital mortality did not differ among ICU-treated pneumonia cases, but SCAP had the best long-term survival.Tiivistelmä Keuhkokuume on yleinen tehohoitoon johtava tulehdussairaus. Suomessa vuonna 2012 teho-osastolla hoidetuista infektioista 51 % oli keuhkoalkuisia. Keuhkokuume luokitellaan hankintapaikan mukaan kotisyntyiseksi (CAP) tai sairaalasyntyiseksi (HAP). Hengityslaitehoitoon liittyvä keuhkokuume (VAP) on sairaalasyntyisen keuhkokuumeen alatyyppi. Vakavalla kotisyntyisellä keuhkokuumeella (SCAP) tarkoitetaan vaikeaa keuhkoinfektiota, joka vaatii hengityslaitehoitoa tai verenkierron tukihoitoa teho-osastolla. SCAP:iin liittyy korkea sairastuvuus sekä tehohoito- ja sairaalakuolleisuus. Tässä havainnoivassa kliinisessä tutkimuksessa selvitettiin SCAP:n kliinistä kuvaa ja ennustetta. Erityishuomion kohteena oli varhaisvaiheessa suoritetun keuhkojen tietokonekerroskuvauksen (CT), keuhkokuumeen aiheuttajamikrobien ja antibimikrobihoidon vaikutus taudin hoitoon ja ennusteeseen sekä tehohoidettujen keuhkokuumepotilaiden pitkäaikaisennuste. Väitöskirja koostuu kolmesta retrospektiivisestä osatyöstä, joissa oli yhteensä 392 SCAP-potilasta. Potilaiden mediaani-ikä oli 55 vuotta ja heistä 55,9 % oli miehiä. Varhaisvaiheen keuhkojen CT:n sekä beetalaktaami-kinoloni- ja beetalaktaami- makrolidi-yhdistelmähoidon vaikutusta keuhkokuumeen hoitoon arvioitiin retrospektiivisesti. SCAP-potilaiden sairaalakuolleisuutta ja pitkäaikaisennustetta verrattiin 25:n VAP- ja 66:n HAP-potilaan ennusteeseen. Prospektiivisessa tutkimuksessa oli 49 hengityskonehoidettua potilasta. Tutkimuksessa tarkasteltiin virusten osuutta ja merkitystä vaikeassa SCAP:ssa. Keuhkojen CT havaitsi 58,5 %:lla SCAP-potilaista löydöksiä, joita ei todettu keuhkojen natiiviröntgentutkimuksessa. Löydökset johtivat toimenpiteisiin 43 %:lla SCAP-potilaista. Happeutumishäiriön vaikeusasteen ja CT:llä todettujen keuhkojen tulehdusmuutosten laajuuden välillä havaittiin yhteys. Virusetiologia on SCAP:ssa yleinen. Viruksia havaittiin 49 %:lla SCAP-potilaista. Beetalaktaami-kinoloni- ja beetalaktaami-makrolidi -yhdistelmähoidon välillä ei havaittu eroa SCAP-potilaiden ennusteessa. SCAP-, HAP- ja VAP-potilaiden ennustevertailussa keuhkokuumetyypin ei todettu vaikuttavan sairaalakuolleisuuteen. Paras yhden vuoden ennuste oli SCAP-potilailla. Yhteenvetona todettakoon, että varhaisvaiheen keuhkojen CT on hyödyllinen SCAP:n hoidossa. Virukset ovat yleisiä SCAP:n aiheuttajamikrobeja. Molemmat tutkitut antimikrobiyhdistelmät todettiin hyviksi SCAP:n hoidossa. Sairaalakuolleisuus ei eroa keuhkokuumealatyyppien välillä, mutta SCAP- potilailla on paras pitkäaikaisennuste

Efficient DNA Packaging of Bacteriophage PRD1 Requires the Unique Vertex Protein P6

The assembly of bacteriophage PRD1 proceeds via formation of empty procapsids containing an internal lipid membrane, into which the linear double-stranded DNA genome is subsequently packaged. The packaging ATPase P9 and other putative packaging proteins have been shown to be located at a unique vertex of the PRD1 capsid. Here, we describe the isolation and characterization of a suppressor-sensitive PRD1 mutant deficient in the unique vertex protein P6. Protein P6 was found to be an essential part of the PRD1 packaging machinery; its absence leads to greatly reduced packaging efficiency. Lack of P6 was not found to affect particle assembly, because in the P6-deficient mutant infection, wild-type (wt) amounts of particles were produced, although most were empty. P6 was determined not to be a specificity factor, as the few filled particles seen in the P6-deficient infection contained only PRD1-specific DNA. The presence of P6 was not necessary for retention of DNA in the capsid once packaging had occurred, and P6-deficient DNA-containing particles were found to be stable and infectious, albeit not as infectious as wt PRD1 virions. A packaging model for bacteriophage PRD1, based on previous results and those obtained in this study, is presented

What is the applicability of a novel surveillance concept of ventilator-associated events?

Abstract Background: In 2013, the Centers for Disease Control and Prevention released a novel surveillance concept called the “ventilator-associated event,” which focused surveillance on objective measures of complications among patients that underwent invasive ventilations. Objective: To evaluate the concordance and possible differences in efficacy (ie, disease severity and outcomes) between 2 surveillance paradigms: (1) infection-related ventilator-associated complications (iVAC) and (2) on conventional ventilator-associated pneumonia (VAP). Design: Prospective, observational, single-center cohort study. Patients: This study included 85 adult patients that received invasive ventilation for at least 2 consecutive calendar days in a 22-bed, adult, mixed medical-surgical intensive care unit in Finland between October 2014 and June 2015. Results: Among these patients, 9 (10.1 per 1,000 days of mechanical ventilation) developed iVAC (10.6%) and 20 (22.4 per 1,000 days of mechanical ventilation) developed conventional VAP (23.5%). The iVAC indicators were most often caused by atelectasis and fluid overload. Compared with patients with conventional VAP, patients with iVAC had significantly worse respiratory status but no other differences in disease severity or outcomes. Conclusions: The incidence of conventional VAP was >2-fold that of iVAC, and the surveillance paradigms for VAP and iVAC capture different patterns of disease. Our results suggest that this novel surveillance concept, although based on objective measures of declining oxygenation, actually identified deteriorations of oxygenation due to noninfectious causes

Interleukin-5, interleukin-6, interferon induced protein-10, procalcitonin and C-reactive protein among mechanically ventilated severe community-acquired viral and bacterial pneumonia patients

Abstract Background: The serum cytokine levels among 45 mechanically ventilated, intensive care unit (ICU)-treated severe community-acquired pneumonia (SCAP) patients with known microbial etiology in three different etiology groups were assessed. Methods: Blood samples for C-reactive protein (CRP), procalcitonin (PCT), interleukin (IL)-5, IL-6, IL-10, human interferon gamma induced protein (IP)-10, and TNF-α (tumor necrosis factor alpha) were collected at time points 0, 12, 24, 48, 72 and 96 h after study inclusion. Results: There were 21 (43%) pure bacterial infections (bacterial group, BG), 5 (10%) pure viral infections (viral group, VG), and 19 (39%) mixed bacterial-viral infections (mixed group, MG) among 45 mechanically ventilated SCAP patients. CRP and PCT levels were significantly higher in the MG and values decreased with time in all groups. PCT differed also in time and group analysis (P = 0.001), the highest being in the MG. IL-5 levels were significantly higher in the VG compared to others (Ptime = 0.001, Pgroup = 0.051 and Ptimexgroup = 0.016). IL-6 and IP-10 levels decreased over time (Ptime = 0.003 and Ptime = 0.021), but there were no differences between groups. Conclusions: SCAP patients with viral etiology have higher IL-5 levels. Patients with mixed viral and bacterial group have higher PCT compared to other etiologies

Successful cryopreservation of dormant buds of blackcurrant (Ribes nigrum L.) by using greenhouse-grown plants and in vitro recovery

Abstract The cryopreservation of dormant buds can be a feasible method for preserving germplasm of cold-tolerant woody plants. In the present study, we evaluated the effects of pre-desiccation, thawing method, and the rehydration of bud sections on the post-cryopreservation recovery of dormant blackcurrant buds in vitro. The estimated recovery of small- and medium-sized buds was 80.1 and 62.7% respectively for desiccated buds and 67.8 and 72.3% respectively for non-desiccated buds. The pre-desiccation of bud sections enhanced the number of the shoots regenerated from vegetative buds (2.3 vs. 4.7). The estimated recovery of fast-thawed buds was better after 14-day than after 7-day rehydration (85 vs. 59%). In slowly thawed buds the difference between 14-day and 7-day rehydration was not significant (73 vs. 62%). The estimated recovery of vegetative and flower buds was 77.7 and 41.1% respectively after 7-day rehydration, and 95.2 and 43.6% respectively after a 14-day rehydration period. The rehydration of bud sections was not necessary for the in vitro recovery of non-desiccated, fast-thawed buds. Of the 23 blackcurrant cultivars cryopreserved using non-desiccated dormant buds collected from a greenhouse, the estimated recovery of 22 cultivars ranged between 42 and 90%

Droplet vitrification technique for cryopreservation of a large diversity of blackcurrant (Ribes nigrum L.) cultivars

Abstract The aim of plant gene banks is to preserve genetic resources selected based on their phenotypic, agronomic, historical or other cultural values for future utilization. In the present study the modified PVS2 droplet vitrification technique was tested and optimized for cryopreservation of a large diversity of blackcurrant (R. nigrum L.) accessions propagated in vitro and selected into a national gene bank core collection. Out of four accessions tested to optimize the method, three recovered and regenerated by 89–97% on average, but one recalcitrant in vitro line only by 25%. The tested post-cryopreservation recovery media with different macronutrient and growth regulator levels showed no generalized effect on regenerated shoots, but the effect of recovery media was different between cultivars. When the whole regeneration chain from cryopreservation via micropropagation to greenhouse conditions was tested, shoots at least 1 cm in length were found necessary for successful transfer ex vitro. The long-term cryopreservation of 22 blackcurrant accessions was finally conducted, with practices slightly modified from the tested protocol. The estimated recovery of shoot tips after 9 weeks in vitro was 17–94% with at least 75% recovery in seven accessions and at least 40% recovery in 19 out of 22 accessions. Only one accession had no cryopreservation success. The results demonstrated that the modified droplet vitrification technique is appropriate for a large diversity of blackcurrant accessions. However, cultivar-related differences and recovery procedures are to be considered for success in regeneration and ex vitro adaptation

The occurrence and spreading of paranasal sinus changes among critically ill patients undergoing invasive ventilation:an observational cohort study

Abstract Background: The development of ventilator-associated pneumonia could be prevented in the nasotracheally intubated patients by a systematic search for and treatment of nosocomial sinusitis. However, the spreading of paranasal sinus changes with time is poorly defined. Purpose: To evaluate the occurrence and spreading of paranasal sinus changes among critically ill patients undergoing invasive ventilation in order to evaluate the association between paranasal changes and Intensive Care Unit (ICU)-related outcomes. Material and methods: This prospective, observational, single-center cohort study was conducted in a single tertiary-level teaching hospital in Finland during 2014–2015. All invasively ventilated adult patients referred for head computed tomography or magnetic resonance imaging scans from October 2014 to June 2015 were eligible for enrolment and monitored daily until discharge from the ICU or death. Results: During the study period, 6.8% (5.7 per 1,000 patient days) of patients had major findings in their maxillary, 20.3% (18.5 per 1,000 patient days) in sphenoidal, 6.8% (5.7 per 1,000 patient days) in ethmoidal, and 3.4% (2.9 per 1,000 patient days) in frontal sinuses. The spreading of paranasal sinus changes doubled in time. In addition, radiographically proved accumulation of fluid was within 39.0%, 35.6%, and 8.6% of maxillary, sphenoidal, and frontal sinuses, respectively. We found no association between ICU-related outcomes and paranasal sinus changes. Conclusion: Paranasal sinus changes were common and progressive among critically ill patients undergoing invasive ventilation, without unfavourable impact on ICU-related outcomes

Association of low mixed venous oxygen saturations during early ICU stay with increased 30-day and 1-year mortality after cardiac surgery:a single-center retrospective study

Abstract Background: Low postoperative mixed venous oxygen saturation (SvO₂) values have been linked to poor outcomes after cardiac surgery. The present study was designed to assess whether SvO₂ values of < 60% at intensive care unit (ICU) admission and 4 h after admission are associated with increased mortality after cardiac surgery. Methods: During the years 2007–2020, 7046 patients (74.4% male; median age, 68 years [interquartile range, 60–74]) underwent cardiac surgery at an academic medical center in Finland. All patients were monitored with a pulmonary artery catheter. SvO₂ values were obtained at ICU admission and 4 h later. Patients were divided into four groups for analyses: SvO₂ ≥ 60% at ICU admission and 4 h later; SvO₂ ≥ 60% at admission but < 60% at 4 h; SvO₂ < 60% at admission but ≥ 60% at 4 h; and SvO₂ < 60% at both ICU admission and 4 h later. Kaplan–Meier survival curves, Cox regression models, and receiver operating characteristic curve analysis were used to assess differences among groups in 30-day and 1-year mortality. Results: In the overall cohort, 52.9% underwent coronary artery bypass grafting (CABG), 29.1% valvular surgery, 12.1% combined CABG and valvular procedures, 3.5% surgery of the ascending aorta or aortic dissection, and 2.4% other cardiac surgery. The 1-year crude mortality was 4.3%. The best outcomes were associated with SvO₂ ≥ 60% at both ICU admission and 4 h later. Hazard ratios for 1-year mortality were highest among patients with SvO₂ <60% at both ICU admission and 4 h later, regardless of surgical subgroup. Conclusions: SvO₂ values < 60% at ICU admission and 4 h after admission are associated with increased 30-day and 1-year mortality after cardiac surgery. Goal-directed therapy protocols targeting SvO₂ ≥ 60% may be beneficial. Prospective studies are needed to confirm these observational findings