Safety and Efficacy of Various Intravenous Insulin Infusion Rates in Patients With and Without Diabetes Presenting With Hypertriglyceridemia.

BACKGROUND: The use of IV insulin infusions in the acute management of hypertriglyceridemia has only been evaluated in small observational studies and case reports. OBJECTIVE: To evaluate the safety and efficacy of IV insulin infusions in the acute management of hypertriglyceridemia. METHODS: This was a retrospective chart review of adult patients who received an IV insulin infusion for the acute management of hypertriglyceridemia. The primary efficacy and safety outcomes were the number of patients who achieved a triglyceride level <500 mg/dL and experienced hypoglycemia (<70 mg/dL), respectively. A subgroup analysis was performed to compare outcomes between patients with and without diabetes, in addition to the IV insulin infusion rate received. RESULTS: In the total population (n = 51), there were no statistically significant differences between the insulin intensity groups in the number of patients who achieved TG levels <500 mg/dL. Compared to patients with a past medical history of diabetes, more patients without a past medical history of diabetes achieved triglyceride levels <500 mg/dL (14% vs 53%, respectively, P < 0.001). The number of hypoglycemic events observed in patients with and without a past medical history of diabetes were 5 (14%) and 4 (27%), respectively (P = 0.023). CONCLUSION AND RELEVANCE: Our findings suggest that patients who present with lower initial TG levels are more likely to achieve TG levels <500 mg/dL. To minimize the risk of hypoglycemia providers should consider prescribing a concomitant dextrose infusion and limiting IV insulin infusion rates ≤ 0.075 units/kg/h.

Approach to the diagnosis and treatment of non-tuberculous mycobacterial disease.

Non-tuberculous mycobacteria (NTM) is a collective name given to a group of more than 190 species of Mycobacterium. The clinical presentation for most NTM infections is non-specific, often resulting in delayed diagnosis. Further complicating matters is that NTM organisms can be difficult to isolate. Medications used to treat NTM infection can be difficult for patients to tolerate, and prolonged courses of anti-mycobacterial therapy are often required for adequate suppression or eradication. Herein, we review different NTM syndromes, appropriate diagnostic tests, and treatment regimens.

Idiopathic pulmonary fibrosis and gastroesophageal reflux disease: A population-based, case-control study.

BACKGROUND: It is unknown whether gastroesophageal reflux disease (GERD) is a risk factor or consequence of idiopathic pulmonary fibrosis (IPF). This study aimed to determine whether patients with IPF were more likely to have GERD compared with age- and sex-matched controls who either had 1) interstitial lung disease (ILD) other than IPF or 2) no diagnosed lung disease (population control). METHODS: We used the medical records-linkage system of the Rochester Epidemiology Project (REP) to identify patients with IPF who resided in Olmsted County, Minnesota, from January 1, 1997, through June 30, 2017. IPF cases were each matched with patients from 2 control groups (non-IPF ILD controls and population controls). We used conditional logistic regression to model associations between GERD diagnosis and IPF case status. P values were adjusted for multiple comparisons by using the Bonferroni adjustment (P values < .025 were considered statistically significant). RESULTS: One hundred thirteen IPF cases were identified and matched to 226 population controls and 226 controls with non-IPF ILD. After multivariable adjustment, the odds of having GERD were 1.78 times higher (95% CI, 1.09-2.91; P = .02) in IPF cases compared with population controls. After multivariable adjustment, the odds of having GERD were 0.46 times lower (95% CI, 0.23-0.94; P = .03) in IPF cases compared with non-IPF ILD controls. CONCLUSION: GERD may be an important contributor to the development of lung fibrosis. Thus, it should be investigated and addressed adequately when detected in patients with IPF and patients with non-IPF ILD.

Exacerbation of Previously Undiagnosed Bird Fancier's Lung by Pembrolizumab Therapy.

Immune checkpoint inhibitors have revolutionized cancer therapy. As the use of checkpoint inhibitors becomes widespread, the early recognition and treatment of their unique spectrum of adverse effects, called immune-related adverse events, become critical. Perhaps the most significant of these is the pulmonary toxicity currently described as "pneumonitis." However, little is known about the effects of immune checkpoint inhibitors on preexisting interstitial lung disease. We present a case of subclinical hypersensitivity pneumonitis that was exacerbated by pembrolizumab, a programmed cell death-1 inhibitor. This case illustrates a new immune-related adverse event and suggests that exacerbation of preexisting interstitial lung disease is a potential pulmonary toxicity from immune checkpoint inhibitor therapy.

Toll-like receptors in mycobacterial infection.

Toll-like receptors are transmembrane glycoproteins predominantly expressed in tissues with immune function. They are considered one of the most important pattern recognition receptor families discovered at the end of 20th century and a key aspect of the innate immune system response to infectious disease. Here we present a review of the current knowledge of individual Toll-like receptors, 1 through 13, with a focus on their role in the immune system response to mycobacterial infection. We present literature to date about the Toll-like receptors structure, localization and expression, signaling pathways, and function. The Toll-like receptor family may have proven an important role in the immune system response to mycobacterial infections, including M. tuberculosis and non-tuberculous (NTM) organisms.

Annexins family: insights into their functions and potential role in pathogenesis of sarcoidosis.

Annexins are Ca(2+)-regulated phospholipid-binding proteins that play an important role in the cell life cycle, exocytosis, and apoptosis. Annexin A11 is one of the oldest vertebrate annexins that has a crucial role in sarcoidosis pathogenesis. The mechanism of effect in sarcoidosis granuloma cells may be due to alterations in apoptosis. Immune cells with a specific mutation at protein location 230 are resistant to apoptosis and consequently have continued effects on inflammation and progression of sarcoidosis. The mechanism of action of annexin A11 may be based upon alterations in delivering calcium to two different apoptosis pathways (caspase and P53).

Annexin A11 is associated with pulmonary fibrosis in African American patients with sarcoidosis.

Not available.

In vitro activity of ramoplanin and comparator drugs against anaerobic intestinal bacteria from the perspective of potential utility in pathology involving bowel flora.

Susceptibility of intestinal bacteria to various antimicrobial agents in vitro, together with levels of those agents achieved in the gut, provides information on the likely impact of the agents on the intestinal flora. Orally administered drugs that are poorly absorbed may be useful for treatment of intestinal infections and for certain other situations in which intestinal bacteria may play a role. The antimicrobial activity of ramoplanin (MDL 62,198) against 928 strains of intestinal anaerobic bacteria was determined using the NCCLS-approved Wadsworth brucella laked-blood agar dilution method. The activity of ramoplanin was compared with that of ampicillin, bacitracin, metronidazole, trimethoprim/sulfamethoxazole (TMP/SMX), and vancomycin. The organisms tested included Bacteroides fragilis group (n=89), other Bacteroides species (n=16), other anaerobic Gram-negative rods (n=56) anaerobic cocci (n=114), Clostridium species (n=426), and non-sporeforming anaerobic Gram-positive rods (n=227). The overall MIC(90)s of ramoplanin, ampicillin, bacitracin, metronidazole, and vancomycin were 256, 32, 128, 16, and 128 mcg/ml, respectively. Ramoplanin was almost always highly active vs. Gram-positive organisms and relatively poor in activity against Gram-negative organisms, particularly Bacteroides, Bilophila, Prevotella, and Veillonella. Vancomycin was quite similar to ramoplanin in its activity. Ampicillin was relatively poor in activity vs. organisms that often produce beta-lactamase, including most of the Gram-negative rods as well as Clostridium bolteae and C. clostridioforme. Bacitracin was relatively poor in activity against most anaerobic Gram-negative rods, but better vs. most Gram-positive organisms. Metronidazole was very active against all groups other than bifidobacteria and some strains of other types of non-sporeforming Gram-positive bacilli. TMP/SMX was very poorly active, with an MIC(90) of >2048 mcg/ml.

Rapid identification of Gram-positive anaerobic coccal species originally classified in the genus Peptostreptococcus by multiplex PCR assays using genus- and species-specific primers.

Here, a rapid and reliable two-step multiplex PCR assay for identifying 14 Gram-positive anaerobic cocci (GPAC) species originally classified in the genus Peptostreptococcus (Anaerococcus hydrogenalis, Anaerococcus lactolyticus, Anaerococcus octavius, Anaerococcus prevotii, Anaerococcus tetradius, Anaerococcus vaginalis, Finegoldia magna, Micromonas micros, Peptostreptococcus anaerobius, Peptoniphilus asaccharolyticus, Peptoniphilus harei, Peptoniphilus indolicus, Peptoniphilus ivorii and Peptoniphilus lacrimalis) is reported. Fourteen type strains representing 14 GPAC species were first identified to the genus level by multiplex PCR (multiplex PCR-G). Since three of these genera (Finegoldia, Micromonas and Peptostreptococcus) contain only a single species, F. magna, M. micros and P. anaerobius, respectively, these organisms were identified to the species level directly by using the multiplex PCR-G. Then six species of the genus Anaerococcus (A. hydrogenalis, A. lactolyticus, A. octavius, A. prevotii, A. vaginalis and A. tetradius) were further identified to the species level using multiplex PCR assays (multiplex PCR-Ia and multiplex PCR-Ib). Similarly, five species of the genus Peptoniphilus (Pn. asaccharolyticus, Pn. harei, Pn. indolicus, Pn. ivorii and Pn. lacrimalis) were identified to the species level using multiplex PCR-IIa and multiplex PCR-IIb. The established two-step multiplex PCR identification scheme was applied to the identification of 190 clinical isolates of GPAC species that had been identified previously to the species level by 16S rRNA sequencing and phenotypic tests. The identification obtained from multiplex PCR assays showed 100 % agreement with 16S rDNA sequencing identification, but only 65 % (123/190) agreement with the identification obtained by phenotypic tests. The multiplex PCR scheme established in this study is a simple, rapid and reliable method for the identification of GPAC species. It will permit a more accurate assessment of the role of various GPAC species in infection and of the degree of antimicrobial resistance in each of the group members.

Rapid identification of the species of the Bacteroides fragilis group by multiplex PCR assays using group- and species-specific primers.

We report a rapid and reliable two-step multiplex polymerase chain reaction (PCR) assay to identify the 10 Bacteroides fragilis group species - Bacteroides caccae, B. distasonis, B. eggerthii, B. fragilis, B. merdae, B. ovatus, B. stercoris, B. thetaiotaomicron, B. uniformis and B. vulgatus. These 10 species were first divided into three subgroups by multiplex PCR-G, followed by three multiplex PCR assays with three species-specific primer mixtures for identification to the species level. The primers were designed from nucleotide sequences of the 16S rRNA, the 16S-23S rRNA intergenic spacer region and part of the 23S rRNA gene. The established two-step multiplex PCR identification scheme was applied to the identification of 155 clinical isolates of the B. fragilis group that were previously identified to the species level by phenotypic tests. The new scheme was more accurate than phenotypic identification, which was accurate only 84.5% of the time. The multiplex PCR scheme established in this study is a simple, rapid and reliable method for the identification of the B. fragilis group species. This will permit more accurate assessment of the role of various B. fragilis group members in infections and of the degree of antimicrobial resistance in each of the group members.

In vitro activities of faropenem against 579 strains of anaerobic bacteria.

The activity of faropenem, a new oral penem, was tested against 579 strains of anaerobic bacteria by using the NCCLS-approved reference method. Drugs tested included amoxicillin-clavulanate, cefoxitin, clindamycin, faropenem, imipenem, and metronidazole. Of the 176 strains of Bacteroides fragilis group isolates tested, two isolates had faropenem MICs of 64 micro g/ml and imipenem MICs of >32 micro g/ml. Faropenem had an MIC of 16 micro g/ml for an additional isolate of B. fragilis; this strain was sensitive to imipenem (MIC of 1 micro g/ml). Both faropenem and imipenem had MICs of < or=4 micro g/ml for all isolates of Bacteroides capillosus (10 isolates), Bacteroides splanchnicus (13 isolates), Bacteroides ureolyticus (11 isolates), Bilophila wadsworthia (11 isolates), Porphyromonas species (42 isolates), Prevotella species (78 isolates), Campylobacter species (25 isolates), Sutterella wadsworthensis (11 isolates), Fusobacterium nucleatum (19 isolates), Fusobacterium mortiferum/varium (20 isolates), and other Fusobacterium species (9 isolates). Faropenem and imipenem had MICs of 16 to 32 micro g/ml for two strains of Clostridium difficile; the MICs for all other strains of Clostridium tested (69 isolates) were < or =4 micro g/ml. Faropenem had MICs of 8 and 16 micro g/ml, respectively, for two strains of Peptostreptococcus anaerobius (MICs of imipenem were 2 micro g/ml). MICs were < or =4 micro g/ml for all other strains of gram-positive anaerobic cocci (53 isolates) and non-spore-forming gram-positive rods (28 isolates). Other results were as expected and reported in previous studies. No metronidazole resistance was seen in gram-negative anaerobes other than S. wadsworthensis (18% resistant); 63% of gram-positive non-spore-forming rods were resistant. Some degree of clindamycin resistance was seen in most of the groups tested.