Demographic and clinical features of critically ill patients with COVID-19 in Greece: The burden of diabetes and obesity.

AIMS: The aim of the study was to investigate the association between type-2 diabetes mellitus, other underlying diseases and obesity with the outcomes of critically ill Covid-19 patients in Greece. METHODS: In this retrospective observational multi-centre study, data and outcomes of 90 RNA 2109-nCoV confirmed critically ill patients from 8 hospitals throughout Greece, were analysed. All reported information stand through April 13th 2020. RESULTS: The median age of the patients was 65.5 (IQR 56-73), majority were male (80%) and obesity was present in 34.4% of patients most prevalent to younger than 55 years. Hypertension was the prevailing comorbidity (50%), followed by cardiovascular diseases (21.1%) and type-2 diabetes (18.9%). At admission, common symptoms duration had a median of 8 (IQR 5-11) days. A 13.3% of the patients were discharged, 53.4% were still in the ICUs and 28.9% deceased who were hospitalised for fewer days than the survivors [6 (IQR 3-9) vs. 9 (IQR 7-14.5) respectively]. Aging was not a risk factor but diabetes deteriorates the outcomes. Obesity poses a suggestive burden as it was more notable in deceased versus survivors. CONCLUSIONS: Type 2 diabetes and obesity may have contributed to disease severity and mortality in COVID-19 critically ill patients in Greece.

Bronchoalveolar Lavage Fluid Cytology in Culture-Documented Invasive Pulmonary Aspergillosis in Patients with Hematologic Diseases: Analysis of 67 Episodes.

There is a paucity of studies on the yield of Gomori-methenamine-silver (GMS) staining in bronchoalveolar lavage (BAL) fluid cytology and its comparison with fluorescent dye staining for the diagnosis of invasive pulmonary aspergillosis (IPA) in patients with hematologic malignancies. To that end, we analyzed the yield of direct fungal visualization in BAL fluid cytology with GMS staining, in a series of culture-positive IPA cases in 67 patients with hematologic malignancies, and we compared the results with those of direct examination with calcofluor white staining and BAL fluid galactomannan assays, when available. GMS staining in BAL fluid cytology was positive in 42% of the 67 cases and revealed coinfections in 7 cases. In contrast, only 2/67 (3.6%) BAL fluid samples were positive in direct smears stained with the fluorescent dye calcofluor white. Positive GMS staining results were significantly more frequent in IPA cases with cavitary lesions and IPA cases caused by >1 Aspergillus species, but the proportions of positive cytology results among Aspergillus species were not different.

Multi-drug resistant organism infections in a medical ICU: Association to clinical features and impact upon outcome.

OBJECTIVE: To define clinical features associated with Intensive Care Unit (ICU) infections caused by multi-drug resistant organisms (MDRO) and their impact on patient outcome. DESIGN: A single-center, retrospective case-control study was carried out between January 2010 and May 2010. SETTING: A medical ICU (MICU) in the United States. PATIENTS: The study included a total of 127 MDRO-positive patients and 186 MDRO-negative patients. INTERVENTIONS: No interventions were carried out. RESULTS: Out of a total of 313 patients, MDROs were present in 127 (41.7%). Based on the multivariate analysis, only infection as a cause of admission [OR 3.3 (1.9-5.8)]), total days of ventilation [OR 1.07 (1.01-1.12)], total days in hospital [OR 1.04 (1.01-1.07)], immunosuppression [OR 2.04 (1.2-3.5)], a history of hyperlipidemia [OR 2.2 (1.2-3.8)], surgical history [OR 1.82 (1.05-3.14)] and age [OR 1.02 (1.00-1.04)] were identified as clinical factors independently associated to MDROs, while the Caucasian race was negatively associated to MDROs. The distribution of days on ventilation, days in hospital and days of antibiotic treatment prior to infection differed between the MDRO-positive and MDRO-negative groups. The MDRO-positive patients showed a greater median number of days in hospital and days of antibiotic treatment before infection, with a greater median number of days in hospital, days of antibiotic treatment and days of ventilation after infection, compared to the MDRO-negative patients. The mortality rate was not significantly different between the two groups. Appropriate empirical antibiotic therapy was prescribed in 82% of the MDRO-positive cases - such treatment being started within 24h after onset of the infection in 68.5% of the cases. CONCLUSION: Defining clinical factors associated with MDRO infections and administering timely and appropriate empirical antibiotic therapy may help reduce the mortality associated with these infections. In our hospital we did not withhold broad spectrum drugs as empirical therapy in patients with clinical features associated to MDRO infection. Our rate of appropriate empirical therapy was therefore high, which could explain the absence of excessive mortality in patients infected with MDROs.

Early response roles for prolactin cortisol and circulating and cellular levels of heat shock proteins 72 and 90α in severe sepsis and SIRS.

OBJECTIVE: To evaluate the early heat shock protein (HSP) and hormonal stress response of intensive care unit (ICU) patients with severe sepsis/septic shock (SS) or systemic inflammatory response syndrome (SIRS) compared to healthy subjects (H). METHODS: Patients with early (first 48 hrs) SS (n = 29) or SIRS (n = 29) admitted to a university ICU and 16 H were enrolled in the study. Serum prolactin, cortisol, and plasma ACTH were determined using immunoassay analyzers. ELISA was used to evaluate extracellular HSPs (eHSP90α, eHSP72) and interleukins. Mean fluorescence intensity (MFI) values for intracellular HSPs (iHSP72, iHSP90α) were measured using 4-colour flow-cytometry. RESULTS: Prolactin, cortisol, and eHSP90α levels were significantly increased in SS patients compared to SIRS and H (P < 0.003). ACTH and eHSP72 were significantly higher in SS and SIRS compared to H (P < 0.005). SS monocytes expressed lower iHSP72 MFI levels compared to H (P = 0.03). Prolactin was related with SAPS III and APACHE II scores and cortisol with eHSP90α, IL-6, and lactate (P < 0.05). In SS and SIRS eHSP90α was related with eHSP72, IL-6, and IL-10. CONCLUSION: Prolactin, apart from cortisol, may have a role in the acute stress response in severe sepsis. In this early-onset inflammatory process, cortisol relates to eHSP90α, monocytes suppress iHSP72, and plasma eHSP72 increases.

Intermittent recruitment with high-frequency oscillation/tracheal gas insufflation in acute respiratory distress syndrome.

In acute respiratory distress syndrome (ARDS), recruitment sessions of high-frequency oscillation (HFO) and tracheal gas insufflation (TGI) with short-lasting recruitment manoeuvres (RMs) may improve oxygenation and enable reduction of subsequent conventional mechanical ventilation (CMV) pressures. We determined the effect of adding HFO-TGI sessions to lung-protective CMV on early/severe ARDS outcome. We conducted a prospective clinical trial, subdivided into a first single-centre period and a second two-centre period. We enrolled 125 (first period, n = 54) patients with arterial oxygen tension (P(a,O(2)))/inspiratory oxygen fraction (F(I,O(2))) of <150 mmHg for >12 consecutive hours at an end-expiratory pressure of ≥ 8 cmH(2)O. Patients were randomly assigned to an HFO-TGI group (receiving HFO-TGI sessions with RMs, interspersed with lung-protective CMV; n = 61) or CMV group (receiving lung-protective CMV and RMs; n = 64). The primary outcome was survival to hospital discharge. Pre-enrolment ventilation duration was variable. During days 1-10 post-randomisation, P(a,O(2))/F(I,O(2))), oxygenation index, plateau pressure and respiratory compliance were improved in the HFO-TGI group versus the CMV group (p < 0.001 for group × time). Within days 1-60, the HFO-TGI group had more ventilator-free days versus the CMV group (median (interquartile range) 31.0 (0.0-42.0) versus 0.0 (0.0-23.0) days; p < 0.001), and more days without respiratory, circulatory, renal, coagulation and liver failure (p ≤ 0.003). Survival to hospital discharge was higher in the HFO-TGI group versus the CMV group (38 (62.3%) out of 61 versus 23 (35.9%) out of 64 subjects; p = 0.004). Intermittent recruitment with HFO-TGI and RMs may improve survival in early/severe ARDS.

HLA and environmental interactions in sarcoidosis.

Sarcoidosis is a systemic granulomatosis of unknown etiology despite being described over 100 years ago. While both genetic predisposition and environmental exposures have been proposed as playing a role in this disease, there have not been any systematic investigations of gene-environmental interaction in this disease. In the ACCESS dataset, detailed environmental histories and high resolution HLA class II typing were performed on 476 cases of newly diagnosed sarcoidosis and 476 matched controls from the patients' community. We evaluated gene-environmental interactions in exposures or HLA class II alleles that were present in > 5% of the population and had an odd ratio of > 1.0. Four exposures and four HLA Class II alleles met these criteria and were evaluated. Significant interaction was observed between HLA DRB1*1101 and insecticide exposure at work (p < 0.10) and suggestive interaction was observed between HLA DRB1*1101 and exposure to mold and musty odors and DRB1*1501 and insecticide exposure at work (P < 0.15). In addition, HLA DRB1*1101 and insecticide exposure at work was associated with extrapulmonary sarcoidosis, specifically cardiac sarcoidosis and hypercalcemia (p<0.05) and HLA DRB1*1101 and exposure to molds and musty odors was associated with pulmonary only sarcoidosis (P < 0.05). These studies suggest that sarcoidosis is due to an interaction of genetic predisposition and environmental exposure in at least some cases of sarcoidosis. Future studies in defined phenotypes of sarcoidosis may be necessary to define environmental and genetic associations with sarcoidosis.

Identification of a novel HLA-DPB1 allele (DPB1*1902) by haplotype-specific extraction and nucleotide sequencing.

The DPB1*1902 allele resulted from a single-nucleotide substitution at codon 35 (TTC --> CTC/F --> L) of exon 2 of DPB1*0402 or 0602.

Outcomes of transplantation with partial T-cell depletion of matched or mismatched unrelated or partially matched related donor bone marrow in children and adolescents with leukemias.

Graft-versus-host disease (GVHD) remains a major barrier to successful hematopoietic stem cell transplant for patients who lack a matched related donor. Partial T-cell depletion (TCD) of the graft may decrease the risk of severe GVHD with unrelated donors (URD) and partially matched related donors (PMRD) while retaining an antileukemic effect. We analyzed our experience using URD and PMRD for pediatric patients with leukemias from 1990 to 2001. A subgroup of 'matched' URD donor pairs was retrospectively analyzed for high-resolution class I. Partial TCD was accomplished with monoclonal antibody T10B9 or OKT3 and complement. There were 76 URD (45% matched) and 28 PMRD recipients. Event-free survival (EFS) was 38.3%, and overall survival (OS) 45.1% at 3 years. On multivariate analysis, there was no difference in survival based upon marrow source, but nonrelapse mortality was higher with the use of PMRD. Relapse occurred in 6% of ALL patients, and 22.8% of AML/MDS patients. Grades III-IV GVHD was observed in only 6.7% of patients. Partial TCD allows use of matched or mismatched URD, or PMRD with little mortality from GVHD, durable engraftment, and no increase in relapse risk.

HLA-B*0811: another example of a single point substitution of the HLA-B*0801 allele.

The described alle HLA-B*0811 is of Caucasoid origin. Most likely it derived from a point mutation of the B*0801 allele at position 559, where an adenine was converted to guanine. This position corresponds to codon 163 and resulted in an amino acid change from threonine to alanine. This substitution may influence both, T-cell interactions and/or peptide binding.

HLA-B*1559: a hybrid allele including exon 2 of HLA-B35 and exon 3 of HLA-B15 and serologically typed as B35.

The new allele HLA-B*1559 described is of Hispanic origin. This allele carries the exon 2 of HLA-B*35 alleles, and is identical to HLA-B*3501 and the exon 3 of HLA-B*1530. Serologically it is typed as B35. The most likely scenario for its generation seems to be a gene conversion event that involved the, frequent in Hispanic populations, B*1522 allele and a B*1530 allele. A segment of the B*1530 allele that included at least the sequences 412-419 would be transferred on a B*1522 background.