Epidemiology and Clinical Outcomes of Fusobacterium Infections: A Six-Year Retrospective Study.

Background and Objectives: Anaerobic bacteria like Fusobacterium can lead to severe and life-threatening infections. The inherent complexities in the isolation of these bacteria may result in diagnostic and therapeutic delays, thereby escalating both morbidity and mortality rates. We aimed to examine data from patients with infections due to Fusobacterium to gain insights into the epidemiology and clinical outcomes of patients with these infections. Methods and Results: We conducted a retrospective analysis of clinical data from a cohort of patients with cultures positive for Fusobacterium species at a tertiary care medical center in the United States. Between 2009 and 2015, we identified 96 patients with cultures positive for Fusobacterium. Patients could be categorized into three groups based on the site of primary infection. Patients with head and neck infections constituted 37% (n 36). Patients with infections of other soft tissue sites accounted for 38.5% (n 37). Patients with anaerobic bacteremia due to Fusobacterium formed 24% (n 23) of the cohort. Surgical intervention coupled with antibiotic therapy emerged as cornerstones of management for patients with head and neck or other soft tissue infections, who generally exhibited more favorable outcomes. Patients with bacteremia were older, more likely to have malignancy, and had a high mortality rate. When speciation was available, Fusobacterium necrophorum was the most frequently isolated species. Conclusions: Our retrospective analysis of epidemiology and clinical outcomes of Fusobacterium infections revealed three distinct cohorts. Patients with head, neck, or soft tissue infections had better outcomes than those with bacteremia. Our findings highlight the importance of employing management strategies based on infection site and underlying comorbidities in patients with Fusobacterium infections. Further research is needed to investigate the optimal therapeutic strategies and identify prognostic indicators to improve clinical outcomes for these complex infections.

The use of selexipag, a prostacyclin receptor analog, for treatment of severe pulmonary artery hypertension during pregnancy, a case report.

Pregnancy in patients with pulmonary artery hypertension (PAH) is associated with high mortality and morbidity. Despite the risks, more patients with PAH are becoming pregnant. Case reports and case series have described the use of IV epoprostenol in these patients with some success. However, there are no published reports regarding the use of oral prostacyclins and prostacyclin receptor agonists in pregnancy. We describe the use of selexipag, an oral prostacyclin receptor agonist, for treating severe PAH during pregnancy in a patient who refused IV prostacyclin therapy. She remained stable throughout pregnancy and delivered a healthy baby girl; however, she died 13 days after her delivery by cesarean section due to developing worsening heart failure. While there is data and support for IV prostacyclins in pregnancy, patients may opt for oral formulations, like in our case. Registry data on the use of oral prostacyclins and prostacyclin receptor agonists in pregnancy may help improve patient outcomes.

Ototoxicity monitoring through the eyes of the treating physician: Perspectives from pulmonology and medical oncology.

OBJECTIVES: Integrating audiological management into the care pathways of clinical specialties that prescribe ototoxic medications for essential, often life-preserving medical care that is critical for early hearing loss identification and remediation. Research shows that successful implementation of a new health service or intervention requires alignment of goals among provider groups, institutional leadership and patients. Thoughtful consideration of the physician's viewpoints about ototoxicity and its implications for treatment planning is, therefore, important for the implementation and enduring success of an ototoxicity monitoring programme (OMP). DESIGN: This discussion paper uses qualitative methods to explore the perspectives of four physicians on OMP provision in their patient populations. STUDY SAMPLE: Three pulmonologists and one oncologist completed the written survey or survey-based interview described in this report. RESULTS: Each physician indicated that (i) ototoxicity is a potential problem for their patients; (ii) monitoring hearing is important to ensure good quality of life among their patients and (iii) treatment modification would be considered if an alternative treatment option were available. The physicians differed in their approaches to ototoxicity monitoring, from routine referrals to audiology, to relying on patient self-referral. CONCLUSION: Physician provider input is needed to optimise monitoring schedules and OMP care coordination with audiology.

Lung function and gas exchange in Eisenmenger syndrome and their impact on exercise capacity and survival.

BACKGROUND: Eisenmenger physiology may contribute to abnormal pulmonary mechanics and gas exchange and thus impaired functional capacity. We explored the relationship between lung function and gas exchange parameters with exercise capacity and survival. METHODS: Stable adult patients with Eisenmenger syndrome (N=32) were prospectively studied using spirometry, lung volumes, diffusion capacity, and blood gas analysis, as well as same day measurement of 6-minute walk distance and cardiopulmonary maximal treadmill exercise. Patients were followed prospectively to determine survival (7.4 ± 0.5 years). Abnormalities were identified and appropriate comparisons were made between affected and unaffected individuals between respiratory mechanics, exercise function, and survival. RESULTS: Obstruction (FEV1/FVC ratio <0.70) was found in 13 patients (41%), who were older but not otherwise different. Restriction was uncommon. Diffusion transfer coefficient, which was <80% in half the patients, correlated with exercise duration (r=0.542, P=0.005), and was worse in non-survivors (N=6). Nearly all patients had a compensated respiratory alkalosis (PaCO2 32 ± 4.4 mm Hg). PaCO2 was less reduced in older patients (r=0.438, P=0.022), and correlated independently with exercise duration (R=-0.463, P=0.03), yet PaO2, not PaCO2, was associated with survival. CONCLUSIONS: Eisenmenger patients show evidence of obstructive lung disease, diffusion abnormalities, and hypocapnia; likely from hyperventilation. Understanding expected lung mechanics and gas exchange may facilitate more appropriate clinical management.

An opportunistic infection associated with ruxolitinib, a novel janus kinase 1,2 inhibitor.

We report a case of Cryptococcus neoformans pneumonia in a patient taking ruxolitinib, a janus kinase 1,2 inhibitor approved for the treatment of myelofibrosis. We hypothesize that ruxolitinib contributed to this infection through its effects on cell-mediated immunity. Clinicians should be aware of the potential for intracellular or opportunistic infections associated with this novel drug class.

Association of interleukin 23 receptor gene with sarcoidosis.

Interleukin 23 receptor (IL23R) gene has been reported as a genetic factor strongly associated with inflammatory bowel disease, psoriasis, and ankylosing spondylitis. We investigated the association between IL23R gene single nucleotide polymorphisms (SNPs) and susceptibility to sarcoidosis, including the clinical manifestation of uveitis. Ninety-one sarcoidosis subjects (58 with and 33 without uveitis) and 104 healthy controls were genotyped for eleven IL23R SNPs. DNA was amplified using specific PCR primers and genotyped by denaturing HPLC and/or direct DNA sequencing. Case-control frequency comparisons were analyzed using Chi square test. Three IL23R SNPs, rs7517847 (intron 6), rs11465804 (intron 8), and rs11209026 (exon 9, c.1142G>A, p.Arg381Gln) were associated with sarcoidosis in our population (p<0.05): rs7517847 showed increased frequencies in sarcoidosis compared to controls, but rs11465804 and rs11209026 were decreased. Two of these SNPs were associated with the uveitis subgroup compared to controls: rs11465804 (0.9% vs. 7.2%, OR=0.11, P=0.013) and rs11209026 (1.8% vs. 7.3%, OR=0.23, P=0.038). This finding indicates the association of IL23R polymorphism with sarcoidosis, especially with sarcoid uveitis. IL23R may be a common susceptibility gene shared by several autoimmune disorders including inflammatory bowel disease, psoriasis, and ankylosing spondylitis and sarcoid uveitis.

Instantaneous within-patient diversity of Pseudomonas aeruginosa quorum-sensing populations from cystic fibrosis lung infections.

In the opportunistic pathogen Pseudomonas aeruginosa, acyl-homoserine lactone (acyl-HSL) quorum sensing (QS) regulates biofilm formation and expression of many extracellular virulence factors. Curiously, QS-deficient variants, often carrying mutations in the central QS regulator LasR, are frequently isolated from infections, particularly from cystic fibrosis (CF) lung infections. Very little is known about the proportion and diversity of these QS variants in individual infections. Such information is desirable to better understand the selective forces that drive the evolution of QS phenotypes, including social cheating and innate (nonsocial) benefits. To obtain insight into the instantaneous within-patient diversity of QS, we assayed a panel of 135 concurrent P. aeruginosa isolates from eight different adult CF patients (9 to 20 isolates per patient) for various QS-controlled phenotypes. Most patients contained complex mixtures of QS-proficient and -deficient isolates. Among all patients, deficiency in individual phenotypes ranged from 0 to about 90%. Acyl-HSL, sequencing, and complementation analyses of variants with global loss-of-function phenotypes revealed dependency upon the central QS circuitry genes lasR, lasI, and rhlI. Deficient and proficient isolates were clonally related, implying evolution from a common ancestor in vivo. Our results show that the diversity of QS types is high within and among patients, suggesting diverse selection pressures in the CF lung. A single selective mechanism, be it of a social or nonsocial nature, is unlikely to account for such heterogeneity. The observed diversity also shows that conclusions about the properties of P. aeruginosa QS populations in individual CF infections cannot be drawn from the characterization of one or a few selected isolates.