Acute Encephalitic Syndrome Induced by Scleromyxedema.

Dermato-neuro syndrome is a potentially fatal neurological complication of scleromyxedema consisting of fever, seizures, and coma. This is an overlooked scleromyxedema case of a 62-year-old female patient from 2-years ago. She was admitted to our ICU because of high fever, colloid speech, muscle ache, and nausea. Molecular methods in the cerebrospinal fluid for neurotropic viruses ruled out acute infectious encephalitis. Her thyroid hormones were within normal values while the serum protein electrophoresis confirmed the monoclonal gammopathy of immunoglobulin G lambda (IgG(λ)), known for the last 2 years. The subsequent bone-marrow biopsy excluded the development of multiple myeloma. The patient fulfilled fundamental diagnostic criteria of scleromyxedema (monoclonal gammopathy, normal thyroid function and the appearance of marked sclerosis and induration of the skin papules on the face, neck, extremities, and skin creases) presenting as dermato-neuro syndrome, which was histologically confirmed. She demonstrated a remarkable improvement after intravenous immunoglobulin treatment during the first 24 hours. Mimics of non-infectious acute encephalitis should include the clinical diagnosis of scleromyxedema, especially when patients present in the emergency department with acute fever, coma, and skin lesions of diffuse sclerodermoid and papular type.

Effect of Early vs. Delayed or No Intubation on Clinical Outcomes of Patients With COVID-19: An Observational Study.

Background: Optimal timing of initiation of invasive mechanical ventilation in patients with acute hypoxemic respiratory failure due to COVID-19 is unknown. Thanks to early flattening of the epidemiological curve, ventilator demand in Greece was kept lower than supply throughout the pandemic, allowing for unbiased comparison of the outcomes of patients undergoing early intubation vs. delayed or no intubation. Methods: We conducted an observational study including all adult patients with laboratory-confirmed COVID-19 consecutively admitted in Evangelismos Hospital, Athens, Greece between March 11, 2020 and April 15, 2020. Patients subsequently admitted in the intensive care unit (ICU) were categorized into the "early intubation" vs. the "delayed or no intubation" group. The "delayed or no intubation" group included patients receiving non-rebreather mask for equal to or more than 24 h or high-flow nasal oxygen for any period of time or non-invasive mechanical ventilation for any period of time in an attempt to avoid intubation. The remaining intubated patients comprised the "early intubation" group. Results: During the study period, a total of 101 patients (37% female, median age 65 years) were admitted in the hospital. Fifty-nine patients (58% of the entire cohort) were exclusively hospitalized in general wards with a mortality of 3% and median length of stay of 7 days. Forty-two patients (19% female, median age 65 years) were admitted in the ICU; all with acute hypoxemic respiratory failure. Of those admitted in the ICU, 62% had at least one comorbidity and 14% were never intubated. Early intubation was not associated with higher ICU-mortality (21 vs. 33%), fewer ventilator-free days (3 vs. 2 days) or fewer ICU-free days than delayed or no intubation. Conclusions: A strategy of early intubation was not associated with worse clinical outcomes compared to delayed or no intubation. Given that early intubation may presumably reduce virus aerosolization, these results may justify further research with a randomized controlled trial.

Corrigendum: Outcomes in Invasive Pulmonary Aspergillosis Infections Complicated by Respiratory Viral Infections in Patients With Hematologic Malignancies: A Case-Control Study.

[This corrects the article DOI: 10.1093/ofid/ofz247.].

Outcomes in Invasive Pulmonary Aspergillosis Infections Complicated by Respiratory Viral Infections in Patients With Hematologic Malignancies: A Case-Control Study.

BACKGROUND: Data regarding invasive pulmonary aspergillosis (IPA) following respiratory viral infections (RVIs) in patients with leukemia and/or hematopoietic stem cell transplantation (LHSCT) are limited. METHODS: We conducted a retrospective case-control study of post-RVI IPA (2006-2016). Cases were patients who underwent LHSCT and had RVI due to respiratory syncytial virus (RSV), influenza virus (INF), or parainfluenza virus (PIV) followed by culture-documented IPA within 6 weeks. Controls had IPA only. RESULTS: We identified 54 cases and 142 controls. Among cases, 29 (54%) had PIV infection, 14 (26%) had INF infection, and 11 (20%) had RSV infection. The median time to IPA after RVI was 7 days. A greater percentage of cases (37 [69%]) than controls (52 [37%]) underwent allogeneic HSCT (P < .0001). Cases were more likely to be nonneutropenic (33 [61%] vs 56 [39%]; P = .009) and in hematologic remission (27 [50%] vs 39 [27%]; P = .003) before IPA. Cases were more likely to have monocytopenia (45 [83%] vs 99 [70%]; P = .05) and less likely to have severe neutropenia (21 [39%] vs 86 [61%]; P = .007) at IPA diagnosis. Prior use of an Aspergillus-active triazole was more common in cases (27 of 28 [96%] vs 50 of 74 [68%]; P = .0017). Median time to empirical antifungal therapy initiation was 2 days in both groups. Crude 42-day mortality rates did not differ between cases (22%) and controls (27%), but the 42-day mortality rate was higher among cases with IPA after RSV infection (45%) than among those with IPA following INF or PIV infection (13%; P = .05). CONCLUSIONS: IPA had comparable outcomes when it followed RVI in patients who underwent LHSCT, and post-RVI IPA occurred more frequently in patients with prior allogeneic HSCT and was associated with leukemia relapse and neutropenia.

Baseline serum Aspergillus galactomannan index in patients with hematologic malignancy and culture-documented invasive pulmonary aspergillosis: is there a difference among Aspergillus species?

It is unclear whether differences exist in baseline serum galactomannan (sGM) in patients with hematologic malignancies and invasive pulmonary aspergillosis (IPA) caused by non-fumigatus Aspergillus species vs Aspergillus fumigatus. We found no differences in baseline sGM positivity rates, median sGM levels, and 42-day mortality in 72 such patients (Aspergillus fumigatus in 43 and non-fumigatus Aspergillus in 29).

Mixed mold pulmonary infections in haematological cancer patients in a tertiary care cancer centre.

There is a paucity of data regarding mixed mold pulmonary infections (MMPIs) in patients with haematological malignancies with or without haematopoietic stem cell transplantation (HSCT). We retrospectively studied 27 such patients (2005-2015) and compared them to patients with invasive pulmonary aspergillosis (IPA) caused by Aspergillus fumigatus. Factors associated with the diagnosis of MMPIs were significant corticosteroid use [20 (74%) vs 6 (22%), P < 0.001], sputum as the source specimen [13 (48%) vs 3 (11%), P = 0.003], younger age (median age: 58 vs 66 years, P = 0.006), and male sex [22 (81%) vs 13 (48%), P = 0.01]. Haematological cancers other than acute myeloid leukaemia (AML)/myelodysplastic syndromes (MDS) were less common in MMPIs than in IPA patients [AML/MDS: 6 (22%) vs 14 (52%), P = 0.04]. Only significant corticosteroid use [95% CI (2.7-42.7), P < 0.001], and sputum as the source specimen [95% (1.6-41.6), P = 0.012] were statistically significant as independently associated with increased risk of MMPIs diagnosis in multivariate analysis. Total mortality rate at day 42 postdiagnosis was comparable in both groups.

Legionnaire's Disease and Influenza.

Legionella pneumophila and influenza types A and B viruses can cause either community-acquired pneumonia with respiratory failure, or Legionella infection could attribute to influenza infection with potentially fatal prognosis. Copathogenesis between pandemic influenza and bacteria is characterized by complex interactions between coinfecting pathogens and the host. Understanding the underlying reason of the emersion of the secondary bacterial infection during an influenza infection is challenging. The dual infection has an impact on viral control and may delay viral clearance. Effective vaccines and antiviral therapy are crucial to increase resistance toward influenza, decrease the prevalence of influenza, and possibly interrupt the potential secondary bacterial infections.

Acute generalized livedo racemosa caused by Capnocytophaga canimorsus identified by MALDI-TOF MS.

Independent of the size of the dog and the type of injury, serious infections may follow a dog bite and these may result in the abrupt onset of multiorgan failure. Early recognition of the warning signs with regard to the underlying severity of the infection is of the utmost importance. Reticulate skin eruptions constitute a precursory phenomenon.

HLA-A and HLA-DRB1 amino acid polymorphisms are associated with susceptibility and protection to pulmonary tuberculosis in a Greek population.

BACKGROUND: Pulmonary tuberculosis remains the single deadliest infectious disease causing high mortality in humans leading to 1.4 million deaths annually. Inherited genetic factors may explain why some people resist infection more successfully than others. METHODS: The polymorphisms of HLA-class I (-A, -B) and class II (-DRB1, -DQB1) genes have been evaluated using DNA-based typing in a population of 86 non-immunosuppressed, unrelated Greek patients with PTb and 46 healthy unrelated people without a history of PTb, who were all tested purified protein derivative positive (>14 mm). RESULTS: The HLA-A R(114) and HLA-DRßN(37) residues are associated with susceptibility. They operate independently from each other and their effect is detected when the population is evaluated for their concurrent presence (A R(114) positive or DRßN(37) positive or A R(114) and DRßN(37) positive). Furthermore the HLA-A S(77) appears to have a protective role, however in the presence of the DRßN(37), the A-S(77) does not exert its protective effect. CONCLUSION: The HLA residues A-S(77), A-R(114) and DRßN(37) in combination with PTb antigenic elements possibly modulate T-cell responses against MTb that lead to either protection or susceptibility. The HLA-A and -DRB1-dependent T-cell networks may interact among themselves and influence each other resulting in different PTb phenotypes.

SNP-specific extraction of haplotype-resolved targeted genomic regions.

The availability of genotyping platforms for comprehensive genetic analysis of complex traits has resulted in a plethora of studies reporting the association of specific single-nucleotide polymorphisms (SNPs) with common diseases or drug responses. However, detailed genetic analysis of these associated regions that would correlate particular polymorphisms to phenotypes has lagged. This is primarily due to the lack of technologies that provide additional sequence information about genomic regions surrounding specific SNPs, preferably in haploid form. Enrichment methods for resequencing should have the specificity to provide DNA linked to SNPs of interest with sufficient quality to be used in a cost-effective and high-throughput manner. We describe a simple, automated method of targeting specific sequences of genomic DNA that can directly be used in downstream applications. The method isolates haploid chromosomal regions flanking targeted SNPs by hybridizing and enzymatically elongating oligonucleotides with biotinylated nucleotides based on their selective binding to unique sequence elements that differentiate one allele from any other differing sequence. The targeted genomic region is captured by streptavidin-coated magnetic particles and analyzed by standard genotyping, sequencing or microarray analysis. We applied this technology to determine contiguous molecular haplotypes across a approximately 150 kb genomic region of the major histocompatibility complex.

Community-acquired methicillin-resistant Staphylococcus aureus carrying Panton-Valentine leukocidin genes: a lethal cause of pneumonia in an adult immunocompetent patient.

Necrotizing pneumonia and fatal septic shock were caused by Panton-Valentine leukocidin-positive, community-acquired, methicillin-resistant Staphylococcus aureus (CA-MRSA) in a previously healthy, 61-y-old female. This patient did not belong to any high-risk group (e.g. homosexuals, military recruits, sports team members, etc.). CA-MRSA infection should be suspected in any adult with severe pneumonia/sepsis.

Whipple's disease: multiple hospital admissions of a man with diarrhoea, fever and arthralgia.

Whipple's disease is a rare chronic multi-systemic infectious disorder caused by the Gram-positive bacillus, Tropheryma whippelii. Infection may involve any organ in the body, and most commonly affects white men in the fourth to sixth decades of life. The most common presenting symptoms are gastrointestinal and include abdominal pain, diarrhoea, anorexia and associated weight loss. However, the variability in presentation is considerable and some patients may present with intermittent low-grade fever, neurological abnormalities (nystagmus, ophthalmoplegia, cranial nerve defects), migratory arthralgia, lymphadenopathy, or involvement of the cardiovascular system. In typical Whipple's disease, the most severe changes are seen in the proximal small intestine and biopsy reveals mucosal and lymph node infiltration with large, foamy histocytes, containing granules that stain positive with periodic acid-Schiff (PAS) reagent and represent intact or partially degraded bacteria. Extended antibiotic treatment (up to 1-year) is indicated. Life-long surveillance for recurrence is essential, once primary treatment has been completed. We report the case of a 58-year-old man who developed a rare infection with the actinobacterium, T. whippelii. The patient had suffered intermittent episodes of varying clinical symptoms associated with multiple hospital admissions and clinical diagnoses, spanning a period of 22 years. Historically, arthralgia was the primary manifestation in this patient and also was the chief complaint for which he was first hospitalized 22 years ago. At his most recent admission to our hospital department, his presenting symptoms were persistent fatigue, weight loss, arthralgia and diarrhoea. Thus, it is essential that clinicians retain a high index of suspicion for T. whippelii infection in patients who have a long-term history of arthritis, fever and diarrhoea.

Identification of HLA-DQalpha and -DRbeta residues associated with susceptibility and protection to epithelial ovarian cancer.

Substantial evidence has been accumulated suggesting that T cells in patients with epithelial ovarian carcinoma (EOC) exhibit an antigen-driven immune response directed against the tumor cells. In the context of human leukocyte antigen (HLA), this suggests its possible involvement in the disease. Therefore, we examined the distribution of the HLA-DRB1*, -DQA1*, and -DQB1* alleles in 47 patients with EOC and 67 healthy Caucasian women. The frequency of D(70) and E(71) polymorphic residues of the DRB1 alleles was significantly reduced in EOC patients versus controls (pD(70)E(71) = 0.009), suggesting a protective role against the disease. The DQalpha residues R(52) and Y(11)R(55) were increased in the patients (p = 0.008 and 0.012, respectively). Because residues 11 and 55 participate in the formation of pocket 1, they may be functionally important amino acid positions that influence disease susceptibility. The frequency of the DQalpha susceptibility epitope (R(52)Y(11)R(55)) among the DRbetaD(70)E(71)-positive EOC patients was increased when compared with DRbetaD(70)E(71)-positive controls (EOC, 100%; control, 52%; p = 0.028). Among individuals without the DQalpha susceptibility epitope, the distribution of DRbetaD(70)E(71)-positive cases was significantly different between EOC patients and controls (EOC, 0%; control, 60%; p = 0.039). Therefore, it appears that the presence of DQalpha susceptibility elements overrides the protective effect of the DRbetaD(70)E(71) epitope and suggests an interactive relationship between DRbeta and DQalpha epitopes that may be of importance for disease susceptibility. Because positions DRbeta 70,71 and DQalpha 52 have been implicated in immunologic diseases, it is likely that besides being critical for T-cell recognition, they may also play a role in T-cell development and acquisition of the T-cell repertoire.

Differential distribution of HLA-DQ beta/DR beta epitopes in the two forms of Guillain-Barré syndrome, acute motor axonal neuropathy and acute inflammatory demyelinating polyneuropathy (AIDP): identification of DQ beta epitopes associated with susceptibility to and protection from AIDP.

Guillain-Barré syndrome (GBS), an acute, immune-mediated paralytic disorder affecting the peripheral nervous system, is the most common cause of acute flaccid paralysis in the post-polio era. GBS is classified into several subtypes based on clinical and pathologic criteria, with acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN) being the most common forms observed. To better understand the pathogenesis of GBS and host susceptibility to developing the disease, the distribution of HLA class II Ags along with the seroreactivity to Campylobacter jejuni were investigated in a population of GBS patients from northern China. Using DNA-based typing methods, 47 patients with AMAN, 25 patients with AIDP, and 97 healthy controls were studied for the distribution of class II alleles. We found that the DQ beta RLD(55-57)/ED(70-71) and DR beta E(9)V(11)H(13) epitopes were associated with susceptibility to AIDP (p = 0.009 and p = 0.004, respectively), and the DQ beta RPD(55-57) epitope was associated with protection (p = 0.05) from AIDP. These DQ beta/DR beta positional residues are a part of pockets 4 (DQ beta 70, 71, DR beta 13), 6 (DR beta 11), and 9 (DQ beta 56, 57, DR beta 9); have been demonstrated to be important in peptide binding and T cell recognition; and are associated with other diseases that have a pathoimmunological basis. Class II HLA associations were not identified with AMAN, suggesting a different immunological mechanism of disease induction in the two forms of GBS. These findings provide immunogenetic evidence for differentiating the two disease entities (AMAN and AIDP) and focuses our attention on particular DR beta/DQ beta residues that may be instrumental in understanding the pathophysiology of AIDP.