The effect of hydrogen gas on the oxidative stress response in adipose tissue.

Oxidative stress in adipose tissue may alter the secretion pattern of adipocytokines and potentially promote atherosclerosis. However, the therapeutic role of hydrogen in adipose tissue under oxidative stress remains unclear. In this study, subcutaneous adipose tissue (SCAT) was collected from the mid-thoracic wounds of 12 patients who underwent open-heart surgery with a mid-thoracic incision. The adipose tissue was then immersed in a culture medium dissolved with hydrogen, which was generated using a hydrogen-generating device. The weight of the adipose tissue was measured before and after hydrogenation, and the tissue was immunostained for nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and superoxide dismutase (SOD), which are markers of oxidative stress. The immunostaining results showed that HO-1 and Nrf2 expression levels were significantly decreased in the hydrogenated group, whereas SOD expression levels increased, but did not attain statistical significance. Image analysis of adipose tissue revealed that a reduction in adipocyte size. Furthermore, hydrogenated adipose tissue showed a trend toward increased gene expression levels of adiponectin and decreased gene expression levels of chemerin, an adipocytokine involved in adipogenesis. These results demonstrated the therapeutic potential of hydrogen gas for oxidative stress in adipose tissue and for reducing adipocyte size.

Fecundity difference is related to the production of reproductive pheromones in rats.

In rodents, male-derived pheromones play fundamental roles in reproduction. The Hirosaki hairless rat (HHR) is a mutant strain derived from the Sprague-Dawley rat (SDR). While investigating the natural mating between single males and females, (SDR♂ x SDR♀) or (HHR♂ x HHR♀), the HHRs showed higher fecundity than the SDRs; the mean period between mating and delivery was shorter and every HHR pair gave birth, whereas approximately half of the SDR pairs gave birth in the 3 months of experimental testing. By changing partners between the HHRs and SDRs, (SDR♂ x HHR♀) or (HHR♂ x SDR♀), we attributed the fecundity difference to males. However, no significant difference was observed in the litter size, the concentration, morphology, or motility of sperm in the cauda epididymis, or the testosterone concentration in the serum between the SDR and HHR males. When an SDR and HHR male were simultaneously mated with a single female, the HHR males always succeeded in leaving progeny. Therefore, we assumed that the reason for the fecundity difference was the difference in copulation efficiency and focused on male-derived pheromones that may induce reproductive behaviors in females. Whereas Darcin (MUP20), one of the pheromones produced in the liver, did not appear to be involved, the extraorbital lacrimal gland (ELG) was heavier in the HHR males and showed larger amounts of pheromones, namely exocrine gland-secreting peptide 1 (ESP1) and cystatin-related protein 1 (CRP1). These results suggest that the fecundity difference is due to the difference in amounts of ELG-derived pheromones.

Expression of opsin and visual cycle-related enzymes in fetal rat skin keratinocytes and cellular response to blue light.

The mechanism by which the skin, a non-visual tissue, responds to light remains unknown. To date, opsin expression has been demonstrated in keratinocytes, melanocytes, and fibroblasts, all of which are skin-derived cells. In this study, we examined whether the visual cycle, by which opsin activity is maintained, is present in skin keratinocytes. We also identified the wavelengths of light to which opsin in keratinocytes responds and explored their effects on skin keratinocytes. The fetal rat skin keratinocytes used in this study expressed OPN2, 3, and 5 in addition to enzymes involved in the visual cycle, and all-trans-retinal, which is produced by exposure to light, was reconverted to 11-cis-retinal, resulting in opsin activation. Using the production of all-trans-retinal after light exposure as an indicator, we discovered that keratinocytes responded to light at 450 nm. Furthermore, actin alpha cardiac muscle 1 expression in keratinocytes was enhanced and cell migration was suppressed by exposure to light at these wavelengths. These results indicate that keratinocytes express various opsins and have a visual cycle that keeps opsin active. Moreover, keratinocytes were shown to respond to the blue/UV region of the light spectrum, suggesting that opsin plays a role in the light response of the skin.

Current insights on social media as a tool for the dissemination of research and education in surgery: a narrative review.

The purpose of our narrative review is to summarize the utilization of social media (SoMe) platforms for research communication within the field of surgery. We searched the PubMed database for articles in the last decade that discuss the utilization of SoMe in surgery and then categorized the diverse purposes of SoMe. SoMe proved to be a powerful tool for disseminating articles. Employing strategic methods like visual abstracts enhances article citation rates, the impact factor, h-index, and Altmetric score (an emerging alternative metric that comprehensively and instantly quantifies the social impact of scientific papers). SoMe also proved valuable for surgical education, with online videos shared widely for surgical training. However, it is essential to acknowledge the associated risk of inconsistency in quality. Moreover, SoMe facilitates discussion on specific topics through hashtags or closed groups and is instrumental in recruiting surgeons, with over half of general surgery residency programs in the US efficiently leveraging these platforms to attract the attention of potential candidates. Thus, there is a wealth of evidence supporting the effective use of SoMe for surgeons. In the contemporary era where SoMe is widely utilized, surgeons should be well-versed in this evidence.

Abnormally Low Alanine Aminotransferase Ameliorated by a Living Donor Liver Transplantation: A Case Report.

Alanine aminotransferase (ALT) is an enzyme that catalyzes the transfer of amino groups from alanine to ketoglutaric acid. ALT is an established marker of liver diseases. Occasionally, ALT levels may be abnormally low due to various factors, making accurate assessment difficult. To date, no studies have documented ALT alterations following Living donor liver transplantation (LDLT) in patients with low ALT levels. Here, we present a case of abnormally low ALT levels that were ameliorated by LDLT. A 27-year-old woman underwent LDLT for refractory cholangitis with biliary atresia. The patient's preoperative ALT level was 1 IU/L. Following graft reperfusion, ALT levels increased (peak value, 456 IU/L), primarily attributed to the donor liver. After LDLT, ALT levels consistently surpassed the lower limit. The differential diagnosis of abnormally low ALT levels suggested a genetic mutation as the most probable underlying cause. Even after LDLT, ALT levels in organs other than the transplanted liver would remain abnormally low. Therefore, to prevent underestimating liver damage, the standard ALT range for such cases should be set lower than the typical range.

A Case of Myocardial Infarction with Non-obstructive Coronary Arteries Complicated by a Ventricular Septal Rupture: The Challenge of Achieving Hemodynamic Stability Using Impella Devices.

The prognosis of myocardial infarction with non-obstructive coronary arteries (MINOCA) is reported to be as worse as myocardial infarction with obstructive coronary arteries. However, its mechanical complications are still poorly understood. A 71-year-old woman developed MINOCA after ascending aortic replacement surgery. During treatment, the patient experienced cardiogenic shock due to a ventricular septal rupture (VSR). The introduction of Impella devices reduced the left-to-right shunt and improved the patient's hemodynamics. Finally, a scheduled surgical repair was performed under stable conditions. In this report, we focused on the pathophysiology of MINOCA-related VSR and discussed the effectiveness of Impella devices as a bridge to surgical repair and circulatory backup during the perioperative period.

Relationship of Thyroid Function with Renal Hemodynamics and Cholesterol Metabolism in Proteinuric Kidney Disease: A Pilot Study.

Nephrotic syndrome and hypothyroidism are respectively reported to influence renal hemodynamics and hypercholesterolemia. However, the relationship of proteinuria-associated thyroid function with renal hemodynamics and cholesterol metabolism has yet to be determined in a simultaneous analysis of thyroid, renal, and cholesterol variables. We investigated the hypothesis that the changes in thyroid hormones by proteinuria may contribute to changes in cholesterol metabolism and renal hemodynamics by proteinuria. Twenty-nine patients (17 men and 12 women) with proteinuric kidney disease (mean age 46 years) were enrolled in a pilot study. Data for serum free triiodothyronine (FT3), free thyroxine (FT4), total cholesterol, and filtration fraction (FF; assessed by para-aminohippuric acid clearance) were used in variable-adjusted correlation analyses. The patients had the following data (mean ± standard deviation): urinary protein 5.18 ± 3.28 g/day, FT3 2.18 ± 0.44 pg/mL, FT4 1.03 ± 0.26 ng/dL, FF 0.27 ± 0.07, and total cholesterol 327 ± 127 mg/dL. There was a significant positive correlation of FT3 with FF (ß = 0.58, p = 0.01) and a significant inverse correlation of FT4 with total cholesterol (ß = -0.40, p = 0.01). A positive correlation of FT3 with FF and an inverse correlation of FT4 with total cholesterol were demonstrated in patients with proteinuric kidney disease. The proteinuria-associated reduction in serum thyroid hormone levels was correlated with hypercholesterolemia and the reduced glomerular FF. Further studies of these relationships are required.

Prevalence of systemic and local risk factors for pulmonary non-tuberculous mycobacterial disease in Japan: a single-institution study.

Objective: To identify the prevalence of risk factors for pulmonary non-tuberculous mycobacterial (NTM) disease in a Japanese population. Patients and Methods: We reviewed 337 consecutive Japanese patients (210 women) with pulmonary NTM disease, including 225 patients with Mycobacterium avium complex (MAC) disease (95.8%) at our hospital during 2006-2017. We calculated the prevalence of risk factors reported in Western countries among mycobacterial species. Results: Pulmonary MAC disease cases comprised 78.2% of pulmonary NTM patients in their 40s, increasing to 100% at age ≥80 years. Body mass index (BMI) was <18.5 in approximately 40% of patients, which was significantly higher than the prevalence of underweight in the Japanese population. The percentage of male heavy smokers (Brinkman index ≥600) was 58.2% of pulmonary NTM disease and was high for all mycobacterial species. In pulmonary MAC disease, systemic factors were observed in the order of malignant tumors (other than lung cancer), diabetes, rheumatoid arthritis, and tuberculosis. Local factors were observed in the order of bronchiectasis, chronic obstructive pulmonary disease, lung cancer, and bronchial asthma. Conclusion: The risk factors reported in Western countries were relatively highly prevalent among Japanese pulmonary NTM disease patients. This observation may help elucidate disease onset mechanisms.

Divided omental flap wrapping a multiple-branched graft replaced with an infected thoracic aortic aneurysm: A case report.

The omental flap is often used to fill the space around the artificial vascular graft as a network sheet to prevent artificial vascular infection. In this study, we report a case in which the omental flap was divided into three parts to fill the dead spaces around the multiple-branched graft, as well as to wrap the suture lines of the graft after graft replacement in a patient with an infected thoracic aorta. An 88-year-old woman was admitted to the hospital with fever and impaired consciousness. Computer tomography revealed an aortic arch aneurysm with enlargement. After emergency stent-graft interpolation and antibiotic treatment, an infected thoracic aortic aneurysm was removed, and a multiple-branched graft replacement of the upper arch was performed. After harvesting an omental flap based on the right gastroepiploic vessels, the omental flap was divided into three on the basis of the epiploic vessels. The middle part of the omental flap was used to fill the space around the lesser curvature of the arch and the distal anastomotic site, the accessory part was used to fill the space between the ascending aorta and the superior caval vein, and the right part was used to wrap the three cervical branches, separately. Fifteen months after surgery, the patient had recovered enough to resume work without any signs of inflammation.

Influences of amino-terminal modifications on amyloid fibril formation of human serum amyloid A.

Human serum amyloid A (SAA) is a precursor protein involved in AA amyloidosis. The N-terminal region of the SAA molecule is crucial for amyloid fibril formation, and therefore modifications in this region are considered to influence the pathogenesis of AA amyloidosis. In the present study, using the N-terminal peptide corresponding to the putative first helix region of the SAA molecule, we investigated the influences of N-terminal modifications on amyloid fibril formation. Spectroscopic analyses revealed that carbamoylation of the N-terminal amino group delayed the onset of amyloid fibril formation. From transmission electron microscopic observations, the N-terminal carbamoylated aggregate showed remarkably different morphologies from the unmodified control. In contrast, acetylation of the N-terminal amino group or truncation of N-terminal amino acid(s) considerably diminished amyloidogenic properties. Furthermore, we also tested the cell toxicity of each peptide aggregate on cultured cells by two cytotoxic assays. Irrespective of carbamoylation or acetylation, MTT assay revealed that SAA peptides reduced the reductive activity of MTT on cells, whereas no apparent increase in LDH release was observed during an LDH assay. In contrast, N-terminal truncation did not affect either MTT reduction or LDH release. These results suggest that N-terminal modification of SAA molecules can act as a switch to regulate susceptibility to AA amyloidosis.

Propensity score analysis comparing off-pump versus on-pump coronary artery bypass grafting in older adults.

OBJECTIVE: This study aimed to compare the results of off-pump and on-pump coronary artery bypass grafting in older adults and to examine early and late outcomes. METHODS: This study included 226 patients aged ≥ 75 years who underwent isolated coronary artery bypass grafting. Of these, 141 and 85 patients were included in the off-pump and on-pump groups, respectively. Propensity scores were calculated for each case, matched, and compared between the two groups (68 cases in each group), along with mid-term outcomes of survival and major adverse cardiac events. RESULTS: Operative time, red blood cell transfusion volume, and postoperative hospital stay duration were significantly higher in the on-pump group (267 vs 370 min, P < 0.001; 4.3 vs 17.2 units, P < 0.001; and 20.8 vs 35.8 days, P = 0.012, respectively). Postoperative occurrence of new atrial fibrillation was significantly higher in the on-pump group (4.4% vs 27.9%, P < 0.001), and Kaplan-Meier survival analysis showed a significantly worse prognosis in the on-pump group than in the off-pump group (3-year survival rate 90.7% vs 71.5%, log rank P = 0.007). However, there was no statistically significant difference in cardiovascular-related deaths (log rank P = 0.07). CONCLUSIONS: On-pump coronary artery bypass grafting in an older adult population resulted in increased transfusion volume and postoperative occurrence of atrial fibrillation. The mid-term postoperative outcomes were also poorer with on-pump coronary artery bypass grafting. Off-pump coronary artery bypass grafting reduced future all-cause deaths in older adults.

Rapid Clinical Improvement of Multicentric Castleman Disease (MCD) with Renal Involvement Following Treatment with Tocilizumab: AA Amyloidosis as a Possible Renal Involvement of MCD.

Castleman disease (CD) is a lymphoproliferative disorder that manifests as hypergammaglobulinemia and severe inflammation with multiorgan involvement. However, renal involvement has been infrequently described in CD. We present a case of a 63-year-old Japanese male patient with multicentric CD (MCD) in whom kidney involvement, including impaired renal function and massive proteinuria, is present. He had a 2-year history of inflammatory arthritis and was referred to our clinic with newly developed proteinuria, renal dysfunction, and elevated levels of acute-phase proteins. Abdominal computed tomography scan revealed hepatosplenomegaly, including mesenteric and inguinal lymph node enlargements. The patient underwent inguinal lymph node resection. Excisional biopsy of the inguinal lymph node showed multiple lymphoid follicles and expansion of interfollicular areas by marked plasmacytosis consistent with mixed type CD. The patient was diagnosed with human herpes virus 8-negative MCD according to the international diagnostic criteria for CD. Diagnostic renal biopsy was not performed following the medical viewpoint. Tocilizumab (TCZ) treatment was highly effective in reducing proteinuria and stabilizing renal function, as well as improving other clinical symptoms. The patient responded to TCZ treatment, and the renal involvement was rapidly improved. Our preliminary immunohistochemical analysis indicated AA amyloid deposits in urinary epithelial cells suggesting a possible renal involvement of AA amyloidosis. TCZ could potentially be one of the therapeutic options in patients with MCD with renal involvement.

Spontaneous regression of lymphovascular invasion and metastasis of malignant melanoma: ultrasound findings.

This report presents a case of malignant melanoma in a 40-year-old male who underwent resection of the tumor in his right ankle. Eleven months after the resection, a subcutaneous mass was observed on his right femur. Ultrasound examination revealed a hypoechoic tubular structure in the right thigh, with a small amount of blood flow in the lesion. Using ultrasound and fine-needle aspiration, the patient was diagnosed with metastasis and lymphovascular invasion of malignant melanoma. Treatment with an immune checkpoint inhibitor was originally scheduled, but the lesion disappeared spontaneously after the fine-needle aspiration.

The effects for inflammatory responses by CPP with different colloidal properties in hemodialysis patients.

Calciprotein particles (CPPs) are colloids composed of solid-phase calcium-phosphate and serum protein fetuin-A. CPPs form a polydispersed system with different particle size and density. CPPs with specific physical properties can induce calcification and innate immune responses in cultured cells. In hemodialysis patients, blood CPP levels were reported to correlate with vascular calcification and inflammation. However, little is known about relation between these disorders and physical properties of CPPs. Here, we show that the association between physical properties of plasma CPPs and serum levels of inflammatory cytokines/chemokines in 78 hemodialysis out-patients by cross-sectional study. Patients with cardiovascular disease (CVD) had significantly higher high density CPP (H-CPP) levels than patients without CVD but not low density CPP (L-CPP). Seven cytokines/chemokines (EGF, eotaxin, IL-8, IP-10, MCP-1, MIP-1, MIP-1ß and TNFα) were detectable in the serum samples from > 95% of the patients. In multivariate regression analysis, H-CPP was positively associated with eotaxin after adjusting for age, gender, smoking, serum phosphate and FGF23. L-CPP was negatively associated with IL-8 after adjusting for age, gender, serum albumin, phosphate and FGF23. High H-CPP levels were associated with pro-inflammatory response, whereas L-CPPs were associated with anti-inflammatory response. CPPs with different physical properties may impact differently on pathophysiology in HD patients.

Membrane translocation of vinculin after UVA exposure facilitates melanosome trafficking.

Skin pigmentation is among the defenses against ultraviolet (UV) radiation. During formation of skin pigmentation, melanosomes that are transported to the cell membrane and released are internalized by keratinocytes. We here examined whether vinculin, the origin of actin fibers, is involved in this intracellular transport of melanosomes by using melanocytes with suppressed vinculin expression. Using fluorescence immunostaining, the migration of vinculin to the cell membrane due to exposure to 365-nm LED light was examined. The intracellular distribution of melanosomes after irradiation was weighted toward the pericellular region compared with non-irradiated cells. With the suppression of vinculin expression, the amount of extracellularly released melanin decreased. We conclude that the membrane migration of vinculin after UVA exposure is involved in the intracellular transport of melanosomes.

Study on the Mechanism of False Low Measurement of IgG-Binding (Affinity) IgM Type M Protein by Turbidimetric Immunoassay.

BACKGROUND: The purpose of this study was to investigate the immunological and physical characteristics of IgM-λ type M-protein from patients who were measured low in the turbidimetric immunoassay (TIA) IgM assay without error codes for high concentration to determine the cause of the false low levels and to clarify the mechanism of their occurrence. METHODS: Materials were IgM patient samples and 8 serum samples from other IgM M-protein patients as controls. Patient samples were assayed by the TIA method, in which five manufacturers and six models (two reagent manufacturers) share the principle, and the BN ProSpec method (nephelometric method), which has a different principle. Dilution linearity tests, IgG addition experiments, isoelectric point electrophoresis, and hydrophobic chromatography were performed on patients and subjects. In addition, the binding capacity of γ-globulin by BIACORE was also examined. RESULTS: The reaction curve of the patient IgM curved downward when the concentration of IgM exceeded 20 g/L, and no error code was obtained. In the measurement by the TIA method of five manufacturers and six models, patient IgM was measured at a false low level with no error code obtained in undiluted dilution by any of the instruments and reagents, but could be measured without any problem by the nephelometric method. In addition, in the patient IgG addition experiment, only patient IgM showed a false low level under high IgG concentration. Furthermore, the binding capacity of patient IgM to γ-globulin (IgG) by BIACORE was significantly higher than that of the control IgM-type M protein. CONCLUSIONS: Patient IgM has an affinity (binding capacity) for IgG and forms an IgM-IgG complex under conditions of high IgG concentration. It was speculated that this complex inhibited the reaction with the anti-IgM antibody and the absorbance of the second reaction did not increase, suggesting a false low.

Low prevalence of SARS-CoV-2 specific antibodies among endoscopists and their assistants in a university hospital in Tochigi prefecture-A single-center study.

Objectives: Gastrointestinal endoscopic procedures have a risk to transmit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) through aerosols. Little information is available on the seroprevalence of SARS-CoV-2 antibodies among healthcare workers (HCWs) in endoscopy units. Thus, the seroprevalence was examined in HCWs who do and do not participate in gastrointestinal endoscopy. Methods: A total of 382 HCWs at Jichi Medical University Hospital were enrolled in this study through March 2021. Among 382 HCWs, 63 are in the endoscopy unit. Serum antibody levels against SARS-CoV-2 were determined by immunochromatography, chemiluminescent immunoassay (CLIA), electric CLIA (ECLIA), and chemiluminescence microparticle immunoassay (CMIA). HCWs in the endoscopy unit underwent testing up to three times. We defined antibody-positive as when at least one test was positive. Results: The seroprevalence of SARS-CoV-2 antibodies in 63 HCWs in the endoscopy unit was 0%-1.9%, 0%-1.7%, and 0%-1.7% during the first (Ap-May 2020), second (Jun-Nov 2020), and third intervals (Dec 2020-Mar 2021), respectively. This seroprevalence was comparable to that of other HCWs not involved with gastrointestinal endoscopy. Two HCWs in the endoscopy unit were positive for antibodies: one was ECLIA-positive and the another was CMIA-positive. The ECLIA-positive HCW was PCR negative and converted to negative for the second and third tests. Another HCW was CMIA-positive at all three evaluations and the titers were unchanged. No HCWs in the endoscopy unit contracted a SARS-CoV-2 infection. Conclusions: The seroprevalence of SARS-CoV-2 antibodies was low among HCWs in the endoscopy unit through March 2021 (UMIN000039997).

Surgical outcomes of acute type A aortic dissection in septuagenarians and octogenarians.

BACKGROUND: We studied surgical outcomes of acute type A aortic dissection and compared early and late outcomes between septuagenarians and octogenarians. METHODS: From 2010 to 2019, we evaluated 254 consecutive patients with acute type A aortic dissection. We performed emergent operations within 48 h of symptom onset for 188 patients, including 59 septuagenarians and 32 octogenarians. RESULTS: The overall 30-day mortality rate was 8.5% in septuagenarians and 9.4% in octogenarians (p = 1.0). The hospital mortality rate was 10.2% in septuagenarians and 12.5% in octogenarians (p = 0.74). Multivariate analysis identified prolonged ventilation (≥ 72 h) as a significant risk factor for hospital mortality. Being an octogenarian was not significantly associated with hospital mortality. The actuarial survival rate at 5 years was 80.1% in septuagenarians and 58.5% in octogenarians (log-rank p = 0.09). The freedom from aortic event rate at 5 years was 91.0% in septuagenarians and 100% in octogenarians (log-rank p = 0.23). CONCLUSION: The two groups showed no significant differences in hospital mortality or morbidity. Our tear-oriented strategies might be appropriate for both septuagenarians and octogenarians. Prolonged ventilation (≥ 72 h) was a significant risk predictor for hospital mortality.

Effects of oral cystine and glutamine on exercise-induced changes in gastrointestinal permeability and damage markers in young men.

PURPOSE: Although acute prolonged strenuous exercise has been shown to increase markers of gastrointestinal permeability and damage, little is known regarding the efficacy of nutritional supplement interventions on the attenuation of exercise-induced gastrointestinal syndrome. This study addressed the effects of oral amino acid supplementation on markers of gastrointestinal permeability and damage in response to exercise. METHODS: Sixteen active men aged 22.7 ± 2.6 years (mean ± standard deviation) completed placebo or cystine and glutamine supplementation trials in random order. Participants received either a placebo or cystine and glutamine supplements, three times a day for 5 days, separated by a 2-week washout period. On day 6, participants took their designated supplements 30 min before running at a speed corresponding to 75% of maximal oxygen uptake for 1 h, followed by a 4-h rest period. Blood samples were collected pre-exercise, immediately post-exercise, 30 min post-exercise, and 1, 2 and 4 h post-exercise on day 6. The plasma lactulose to mannitol ratio (L:M) and plasma intestinal fatty acid-binding protein (I-FABP) were used as markers of gastrointestinal permeability and damage, respectively. RESULTS: Plasma L:M (linear mixed model, coefficient ± standard error: - 0.011 ± 0.004, P = 0.0090) and changes (i.e., from pre-exercise) in plasma I-FABP (linear mixed model, - 195.3 ± 65.7 coefficient ± standard error (pg/mL), P = 0.0035) were lower in the cystine and glutamine supplementation trial than in the placebo trial. CONCLUSION: Oral cystine and glutamine supplementation attenuated the markers of gastrointestinal permeability and damage after 1 h of strenuous running in young men. TRIAL REGISTRATION NUMBER: UMIN000026008. DATE OF REGISTRATION: 13 December 2018.

Additional effect of azithromycin over ß-lactam alone for severe community-acquired pneumonia-associated acute respiratory distress syndrome: a retrospective cohort study.

BACKGROUND: Community-acquired pneumonia (CAP) is the most common cause of acute respiratory distress syndrome (ARDS). Although previous studies have suggested that macrolide therapy is beneficial for ARDS, its benefit for severe CAP-associated ARDS remains uncertain. Previous studies were limited in that they had a small sample size and included patients with non-pulmonary ARDS and those with pulmonary ARDS. This study aimed to investigate the additional effect of azithromycin when used with ß-lactam compared with the effect of ß-lactam alone in mechanically ventilated patients with CAP-associated ARDS. METHODS: We identified mechanically ventilated patients with CAP-associated ARDS between July 2010 and March 2015 using data in the Diagnosis Procedure Combination database, a Japanese nationwide inpatient database. We performed propensity score matching analysis to assess 28-day mortality and in-hospital mortality in mechanically ventilated patients with CAP-associated ARDS who received ß-lactam with and without azithromycin within hospital 2 days after admission. The inverse probability of treatment weighting analysis was also conducted. RESULTS: Eligible patients (n = 1257) were divided into the azithromycin group (n = 226) and the control group (n = 1031). The one-to-four propensity score matching analysis included 139 azithromycin users and 556 non-users. No significant difference was observed between the groups with respect to 28-day mortality (34.5% vs. 37.6%, p = 0.556) or in-hospital mortality (46.0% vs. 49.1%, p = 0.569). The inverse probability of treatment weighting analysis showed similar results. CONCLUSIONS: Compared with treatment with ß-lactam alone, treatment with azithromycin plus ß-lactam had no significant additional effect on 28-day mortality or in-hospital mortality in mechanically ventilated patients with CAP-associated ARDS. To the best of our knowledge, this study is the first to determine the effect of azithromycin in mechanically ventilated patients with CAP-associated ARDS.