Incidence, outcomes, and risk factors of postlaparoscopic subcutaneous emphysema: a historical cohort study.

PURPOSE: Subcutaneous emphysema is a common complication of laparoscopic surgery. We aimed to determine the incidence, outcomes, and risk factors of postlaparoscopic subcutaneous emphysema. METHODS: We conducted a single-centre historical cohort study of adult patients who underwent laparoscopic surgery at Kagoshima University Hospital between 1 April 2018 and 31 March 2021. We used multivariable logistic regression analysis to identify independent factors associated with postlaparoscopic subcutaneous emphysema. RESULTS: We included 1,642 patients with a median [interquartile range] age of 65 [53-72] yr. Postlaparoscopic subcutaneous emphysema was diagnosed in 600 (37%) patients. Female sex (odds ratio [OR], 1.82; 99.5% confidence interval [CI], 1.29 to 2.58), peak end-tidal carbon dioxide ≥ 45 mm Hg (OR, 2.07; 99.5% CI, 1.43 to2.98), and use of the AirSeal® Intelligent Flow System (CONMED Corp., Largo, FL, USA) (OR, 3.37; 99.5% CI, 2.34 to 4.87) were independent factors associated with postlaparoscopic subcutaneous emphysema. In addition, a lower body mass index was significantly associated with increased postlaparoscopic subcutaneous emphysema (P for trend < 0.001). No complications were associated with postlaparoscopic subcutaneous emphysema. CONCLUSIONS: This historical cohort study showed a relatively high incidence of postlaparoscopic subcutaneous emphysema. In addition to previously reported risk factors, female sex and use of the AirSeal Intelligent Flow System were found to be associated with postlaparoscopic subcutaneous emphysema.

RéSUMé: OBJECTIF: L'emphysème sous-cutané est une complication fréquente de la chirurgie laparoscopique. Cette étude visait à déterminer l'incidence, les issues et les facteurs de risque de l'emphysème sous-cutané postlaparoscopique. MéTHODE: Nous avons mené une étude de cohorte historique monocentrique de patient·es adultes ayant bénéficié d'une chirurgie laparoscopique à l'hôpital universitaire de Kagoshima entre le 1er avril 2018 et le 31 mars 2021. Nous avons utilisé une analyse de régression logistique multivariée afin d'identifier les facteurs indépendants associés à l'emphysème sous-cutané postlaparoscopique. RéSULTATS: Nous avons inclus 1642 patient·es d'un âge médian [écart interquartile] de 65 [53-72] ans. L'emphysème sous-cutané postlaparoscopique a été diagnostiqué chez 600 (37 %) personnes. Le sexe féminin (rapport de cotes [RC], 1,82; intervalle de confiance [IC] à 99,5 %, 1,29 à 2,58), un pic télé-expiratoire en CO2 maximale ≥ 45 mm Hg (RC, 2,07; IC 99,5 %, 1,43 à 2,98) et l'utilisation du système AirSeal® Intelligent Flow System (CONMED Corp., Largo, FL, États-Unis) (RC, 3,37; IC 99,5 %, 2,34 à 4,87) étaient des facteurs indépendants associés à l'emphysème sous-cutané postlaparoscopique. De plus, un indice de masse corporelle plus faible était significativement associé à une augmentation de l'emphysème sous-cutané postlaparoscopique (P pour tendance < 0,001). Aucune complication n'a été associée à l'emphysème sous-cutané postlaparoscopique. CONCLUSION: Cette étude de cohorte historique a montré une incidence relativement élevée d'emphysème sous-cutané postlaparoscopique. En plus des facteurs de risque précédemment signalés, le sexe féminin et l'utilisation du système de flux intelligent AirSeal étaient associés à l'emphysème sous-cutané postlaparoscopique.

Lipoprotein glomerulopathy with a novel apolipoprotein E variant, APOE Kanto (Asp 151dup).

A 33-year-old Japanese man was admitted for possible kidney disease because of massive proteinuria. Laboratory findings were characterized by marked urinary protein of 4.7 g/day and high-serum triglyceride levels of 266 mg/dL. Renal biopsy revealed segmental proliferation in the mesangium and lipoprotein thrombi in the glomerular capillary. These results suggested that the diagnosis was lipoprotein glomerulopathy (LPG), although serum apolipoprotein E (apo E) levels were within normal ranges. The APOE phenotype was identified as E2/3 by isoelectric focusing polyacrylamide gel electrophoresis. Direct DNA sequencing analyses for apo E identified a duplication of amino acid 151, aspartic acid, and the gene mutation was named APOE Kanto. APOE gene mutations due to amino acid duplication are rare, and this is the first report showing that amino acid duplication among apo E gene mutations is involved in LPG. It is also noteworthy that the patient developed end-stage kidney disease after over than 10 years despite fibrate treatment.

Identification of hypothermia-inducing neurons in the preoptic area and activation of them by isoflurane anesthesia and central injection of adenosine.

Hibernation and torpor are not passive responses caused by external temperature drops and fasting but are active brain functions that lower body temperature. A population of neurons in the preoptic area was recently identified as such active torpor-regulating neurons. We hypothesized that the other hypothermia-inducing maneuvers would also activate these neurons. To test our hypothesis, we first refined the previous observations, examined the brain regions explicitly activated during the falling phase of body temperature using c-Fos expression, and confirmed the preoptic area. Next, we observed long-lasting hypothermia by reactivating torpor-tagged Gq-expressing neurons using the activity tagging and DREADD systems. Finally, we found that about 40-60% of torpor-tagged neurons were activated by succeeding isoflurane anesthesia and by icv administration of an adenosine A1 agonist. Isoflurane-induced and central adenosine-induced hypothermia is, at least in part, an active process mediated by the torpor-regulating neurons in the preoptic area.

A highly efficient catalytic method for the synthesis of phosphite diesters.

In contrast to conventional methods that rely on stoichiometric activation of phosphonylating reagents, we have developed a highly efficient catalytic method for the synthesis of phosphite diesters using a readily available phosphonylation reagent and alcohols with environmentally benign Zn(ii) catalysts. Two alcohols could be introduced consecutively on the P center with release of trifluoroethanol as the sole byproduct, without any additive, under mild conditions. The products could be oxidized smoothly to access phosphate triesters. A range of alcohols, including sterically demanding and highly functionalized alcohols such as carbohydrates and nucleosides, can be applied in this reaction.

Lipoprotein glomerulopathy with markedly increased arterial stiffness successfully treated with a combination of fenofibrate and losartan: a case report.

BACKGROUND: Lipoprotein glomerulopathy (LPG) is a apolipoprotein E (ApoE)-related glomerular disease and has been associated with type III hyperlipidemia. Without appropriate treatment, chronic kidney disease (CKD) caused by LPG progresses, and approximately half of the patients develop end-stage kidney disease within 1-27 years of disease onset. However, few studies have highlighted the clinical course of cardiovascular diseases (CVDs) in patients with LPG. Herein, we report the first case of LPG in which the CVD risk was assessed using arterial stiffness. CASE PRESENTATION: A 32-year-old Japanese man was referred to our hospital due to persistent proteinuria. Kidney biopsy showed markedly dilated capillary lumens containing pale-stained thrombi, which stained positively with Oil Red O. Electron microscopy revealed the presence of thrombi in the capillary lumen with low electron density and vacuoles of various sizes in part of the thrombi. Toluidine blue and Sudan IV stains were used to stain the thin sections of Epon-embedded tissue samples for electron microscopy. Sudan IV-positive droplets were observed in the capillary lumens, vascular walls, and cytoplasm of tubular cells. Increased serum ApoE concentration was observed. Liquid chromatography-tandem mass spectrometry of laser-microdissected glomeruli from paraffin sections revealed an increase in ApoE. Direct deoxyribonucleic acid sequencing of ApoE revealed a heterozygous ApoE Sendai mutation (Arg145Pro). The patient was finally diagnosed with LPG with heterozygosity for ApoE-Sendai mutation (Arg145Pro). Notably, at the time of diagnosis, he had markedly increased arterial stiffness for his age. Arterial stiffness was measured using brachial-ankle pulse wave velocity (baPWV), which was equivalent to that of a 56-year-old man. After three months of treatment with fenofibrate and losartan, a significant reduction in proteinuria was achieved along with an improvement in baPWV. Furthermore, these effects were maintained despite the lack of decrease in serum ApoE levels. CONCLUSION: Herein, we report the case of a patient with LPG with markedly increased arterial stiffness at the time of diagnosis, in whom combination therapy with fenofibrate and losartan successfully improved proteinuria and arterial stiffness. To the best of our knowledge, this is the first case report of LPG in which CVD risk was assessed using arterial stiffness.

Successful neurolytic thoracic sympathetic ganglion block using C-arm fluoroscopic cone-beam computed tomography in patients with postmastectomy pain syndrome: a report of 3 cases.

BACKGROUND: Postmastectomy pain syndrome involves persistent neuropathic and sympathetically maintained neuropathic pain that can be improved using a thoracic sympathetic ganglion block. However, conventional fluoroscopic procedures pose technical difficulties and are associated with potential severe complications. We report the use of C-arm fluoroscopic cone-beam computed tomography to enhance procedural success and treatment safety. CASE PRESENTATION: Three women diagnosed with postmastectomy pain syndrome and experiencing persistent pain underwent C-arm fluoroscopic cone-beam computed tomography-assisted ethanol neurolytic thoracic sympathetic ganglion block. Pain severity decreased substantially after the procedure. The therapeutic effects were sustained for 12 months in cases 1 and 2 and for 5 months in case 3. All patients experienced a remarkable decrease in allodynia and hyperalgesia intensities. CONCLUSION: C-arm fluoroscopic cone-beam computed tomography-assisted neurolytic thoracic sympathetic ganglion block offers a valuable alternative for managing otherwise intractable postmastectomy pain syndrome before considering more invasive techniques.

Emerging resistance to beta-lactams in Pantoea ananatis isolated from an immunocompetent patient with bacteremia.

We observed an emerging resistance to ß-lactams in a P. ananatis bacteremia case. Whole genome sequence analysis detected two ß-lactamase genes as well as related genes that regulate the ß-lactamase genes in the chromosome. The induction experiment resulted in the expression of the class A ß-lactamase gene in the isolate.

A Continuous Murmur as the Only Clinical Sign for Complex Coronary Artery Fistulas Diagnosis.

An asymptomatic patient presented at our hospital exhibiting a Brugada electrocardiography pattern with coronary artery fistulas. Coronary artery fistula is a congenital or acquired rare abnormal condition with increased symptoms and complications over time. In the absence of the therapeutic consensus, we discuss the association and management for this condition. (Level of Difficulty: Advanced.).

Analysis of the diagnostic capabilities of urinary neutrophil gelatinase-associated lipocalin and serum procalcitonin for acute kidney injury at the early stage of critical care intensive care unit admission.

BACKGROUND: Acute kidney injury (AKI) is a disease that negatively affects patient prognosis and requires early diagnosis and treatment. Biomarkers that predict AKI are needed for early diagnosis of this disease. METHODS: We compared the AKI group and the non-AKI group in patients who were admitted to our critical care intensive care unit (ICU) and conducted a comparative study focusing on urinary neutrophil gelatinase-associated lipocalin (U-NGAL) and serum procalcitonin (PCT). RESULTS: Seventy-one out of 106 ICU inpatients were diagnosed with AKI in accordance with the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. Among the patients who were diagnosed with AKI stages 1 to 3, 94.4% of all patients reached the maximum stage by day 5 after admission. Comparing the non-AKI group and AKI stage 1 to 3 on days 1 to 3 after admission, U-NGAL and PCT levels in the stage 3 group were significantly higher than those in the non-AKI group. Additionally, in receiver operating characteristic curve (ROC) analysis on days 1-3 after admission, U-NGAL and PCT levels can be used as biomarkers for the diagnosis of AKI, and in particular, AKI stage 3 can be predicted and diagnosed with high accuracy. U-NGAL and PCT levels were also significantly higher in AKI due to sepsis and acute pancreatitis and due to sepsis, respectively. CONCLUSIONS: Measuring U-NGAL and PCT levels as biomarkers for AKI may further improve the accuracy of AKI diagnosis in critical care ICU.

Development of risk factor-based scoring system for detection of hypervirulent Klebsiella pneumoniae bloodstream infections.

BACKGROUND: Hypervirulent Klebsiella pneumoniae (HVKp) infections have distinct clinical manifestations from classical K. pneumoniae infections. The hallmark of HVKp infections are liver abscess formation and metastatic infections. Due to the severe sequelae of these complications, method to identify patients at-risk of HVKp infections should be developed. RESULTS: A retrospective cohort study of 222 patients with K. pneumoniae bloodstream infections (BSIs) was performed. Patient demographics, clinical manifestations, and bacterial characteristics were investigated. Ten cases of liver abscesses were identified. Characteristics such as community-onset BSIs, hypermucoviscosity phenotype, and capsular serotype K1 were identified as risk factors for HVKp infections. A scoring system was developed based on the risk factors. The area under the receiver operating characteristic curve for the scoring system was 0.90. A score of ≥ 2 points provided sensitivity and specificity of 0.70 and 0.94, respectively. CONCLUSIONS: Simple scoring system was developed for the diagnosis of HVKp infections. The system allows early identification of patients with K. pneumoniae BSIs in whom hypervirulent infections should be evaluated. Prospective evaluation is expected.

Variants of Lipid-Related Genes in Adult Japanese Patients with Severe Hypertriglyceridemia.

AIM: Hypertriglyceridemia is a type of dyslipidemia that contributes to atherosclerosis and coronary heart disease. Variants in lipoprotein lipase (LPL), apolipoprotein CII (APOC2), apolipoprotein AV (APOA5), glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), lipase maturation factor 1 (LMF1), and glucokinase regulator (GCKR) are responsible for hypertriglyceridemia. We investigated the molecular basis of severe hypertriglyceridemia in adult patients referred to the Clinical Laboratory at Fukuoka University Hospital. METHODS: Twenty-three adult patients with severe hypertriglyceridemia (＞1,000 mg/dL, 11.29 mmol/L) were selected. The coding regions of candidate genes were sequenced by next-generation sequencing. Forty-nine genes reportedly associated with hypertriglyceridemia were analyzed. RESULTS: In the 23 patients, we detected 70 variants: 28 rare and 42 common ones. Among the 28 rare variants with ＜1% allele frequency, p.I4533L in APOB, p.M490I in MLXIPL, p.L152M in NCAN, and p.S264T in TIMD4 were novel. We did not observe single gene homozygous or compound heterozygous disease-causing rare variants in any of the 23 hypertriglyceridemia cases. However, in silico algorithms and previous reports indicated that five rare variants, APOA5 (p.T184S), GCKR (c.354＋1G＞A), LMF1 (p.G410R), and LRP1 (p.G813R; p.R2173Q), and seven common variants, APOA5 (pG185C), APOE (p.C130R; p.E262K/p.E263K), GCKR (p.V103M), GPIHBP1 (p.C14F), LRP1 (p.Y4054F), and MLXIPL (p.Q241H), can cause hypertriglyceridemia. However, all five disease-causing rare variants detected in this study were heterozygous. CONCLUSIONS: The prevalence of disease-causing rare variants in candidate genes in severe hypertriglyceridemia patients was low. The major causes of severe hypertriglyceridemia were not single gene abnormalities, but involved multiple gene variations and environmental factors.

Correction to: Randomized trial of an increased dose of calcium channel blocker or angiotensin II type 1 receptor blocker as an add-on intensive depressor therapy in type 2 diabetes mellitus patients with uncontrolled essential hypertension: the ACADEMIE Study.

In the Original publication of the article, the legend appearing inside the flow chart has been incorrectly published.

Apolipoprotein E-related glomerular disorders.

Of the glomerular disorders that occur due to apolipoprotein E (apoE) mutations, apoE2 homozygote glomerulopathy and lipoprotein glomerulopathy (LPG) have been characterized. ApoE2 homozygote glomerulopathy has been found in individuals expressing homozygous apoE2/2. This was characterized histologically by glomerulosclerosis with marked infiltration of foam cells derived from macrophages, and occasionally with non-lamellated lipoprotein thrombi. Recently, several cases of apoE Toyonaka (Ser197Cys) combined with homozygous apoE2/2 have been reported, in which non-immune membranous nephropathy-like features were observed in glomeruli. Interestingly, in these cases, apoE accumulation was identified by tandem mass spectrometry. Therefore, it is speculated that these findings may arise from apoE molecules without lipids, which result from hinge damage by apoE Toyonaka and may cross the glomerular basement membrane as small molecules. LPG is primarily associated with heterozygous apoE mutations surrounding the low-density lipoprotein-receptor binding site, and it is histologically characterized by lamellated lipoprotein thrombi that lack foam cells. Recent studies have suggested that LPG can be induced by thermodynamic destabilization, hydrophobic surface exposure, and the aggregation of apoE resulting from the incompatibility of apoE mutated residues within helical regions. Additionally, apoE5 may play a supporting role in the development of LPG and in lipid-induced kidney diseases via hyperlipoproteinemia. Thus, it is interesting that many apoE mutations contribute to characteristic glomerular disorders through various mechanisms. In particular, macrophages may uptake lipoproteins into the cytoplasm and contribute to the development of apoE2 homozygote glomerulopathy as foam cells, and their dysfunction may contribute to the accumulation of lipoproteins in the glomerulus, causing lipoprotein thrombi in LPG.

Comparison of Two Homogeneous LDL-Cholesterol Assays Using Fresh Hypertriglyceridemic Serum and Quantitative Ultracentrifugation Fractions.

AIM: The purpose of this study was to compare two homogeneous assays of low-density lipoprotein-cholesterol (LDL-C) with a modified beta quantification reference measurement for LDL-C (BQ-LDL), fractions of chylomicron (CM), very low-density lipoprotein (VLDL) and intermediate-density lipoprotein (IDL) by quantitative ultracentrifugation in patients with hypertriglyceridemia. METHODS: Two homogeneous LDL-C assays (LDL-C(K), Kyowa Medex and LDL-C(S), Sekisui Medical) were used to measure 198 samples of fresh anonymized leftover sera with hypertriglyceridemia (≥ 150 mg/dL). Of these, 32 samples with discrepant LDL-C levels or hypertriglyceridemia (≥ 400 mg/dL) were used for further analysis. Quantitative ultracentrifugation was used to separate samples. RESULTS: The two homogeneous LDL-C assays had a strong correlation with each other for the samples from 198 patients with hypertriglyceridemia. LDL-C(K) and LDL-C(S) in 32 selected samples were strongly correlated with BQ-LDL. In both homogeneous assays, cholesterol in the CM and VLDL fractions was measured as part of the LDL-C. A weak correlation was found between cholesterol in the VLDL fraction and LDL-C using the two homogeneous assays, but no correlation was found with cholesterol in the CM fraction. Cholesterol in the IDL fraction was also measured as part of the LDL-C in both assays. CONCLUSION: Both homogeneous assays partially detected cholesterol in the chylomicron and VLDL fractions, but LDL-C measured by both homogeneous assays correlated with BQ-LDL.

A case of apolipoprotein E Toyonaka and homozygous apolipoprotein E2/2 showing non-immune membranous nephropathy-like glomerular lesions with foamy changes.

A 47-year-old Japanese man with mild proteinuria was treated with an ACE inhibitor and antiplatelet agent for 7 years. However, urinary protein levels increased and renal biopsy was performed. Eight out of 20 glomeruli showed global or segmental sclerosis with foamy changes or bubbles, but with a different appearance to typical foam cells or lipoprotein thrombi. "Spike" formation, as observed in membranous nephropathy (MN), was segmentally detected in methenamine silver-stained sections. In an immunofluorescence study, weak linear patterns for IgG and scanty deposits for C3 were observed in glomeruli, but were not specific for immunogenetic MN. An electron microscopy study showed highly dense deposits in the subepithelial, subendothelial, and mesangial areas, in which microbubbles appeared under a higher magnification. Since this case exhibited hypertriglyceridemia and cholesterolemia with high serum apolipoprotein E (apoE) clinically and homozygous apoE2/2 by apoE phenotype and genotype analyses, apoE2 homozygote glomerulopathy was diagnosed and various lipid-lowering agents, e.g., probucol, fenofibrate, and ezetimibe, were administered. However, renal dysfunction gradually developed and peritoneal dialysis was initiated 11 years after the diagnosis. ApoE Toyonaka (Ser197Cys) and homozygous E2/2 were recently identified by direct DNA sequencing. Therefore, non-immune MN-like lesions may develop with the combination of these apoE mutations.

Randomized trial of an increased dose of calcium channel blocker or angiotensin II type 1 receptor blocker as an add-on intensive depressor therapy in type 2 diabetes mellitus patients with uncontrolled essential hypertension: the ACADEMIE Study.

There is a lack of data on how to treat hypertensive patients with diabetes when treatment with medium doses of calcium channel blocker and angiotensin II type 1 receptor blocker (ARB) is insufficient to achieve the target blood pressure (BP). A total of 121 participants with type 2 diabetes and uncontrolled essential hypertension, who were receiving medium doses of amlodipine (5 mg/day) and ARB, were enrolled. Participants were randomized to receive either a high dose of amlodipine (10 mg/day) plus a medium dose of ARB (high-AML) or a medium dose of amlodipine (5 mg/day) plus a high dose of ARB (high-ARB). The depressor effects of these two regimens were monitored using a telemonitoring home BP-measuring system. Fifty-four patients were excluded after an observation period, and the remaining 67 eligible participants were randomized into the two groups; 42 which had a record of their home BP for analysis. The change in morning home systolic and diastolic BP was greater in the high-AML than in the high-ARB (systolic BP; - 7.9 mmHg vs. + 2.7 mmHg; p = 0.0002, diastolic BP; - 3.9 mmHg vs. + 0.6 mmHg; p = 0.0007). In addition, the home systolic and diastolic BP before going to bed and office systolic BP were significantly reduced from week 0 only in the high-AML. An increased dose of amlodipine, but not ARB, reduced home morning BP in hypertensive patients with type 2 diabetes who were already receiving combination therapy with medium doses of amlodipine and ARB.

The effects of hemodynamic management using the trend of the perfusion index and pulse pressure variation on tissue perfusion: a randomized pilot study.

BACKGROUND: Intraoperative hemodynamic management is challenging because precise assessment of the adequacy of the intravascular volume is difficult during surgery. Perfusion index (PI) has been shown to reflect changes in peripheral circulation perfusion. Pulse pressure variation (PPV) reflects the preload responsiveness. The hypothesis of this study was that hemodynamic management using the trend of the PI and PPV would improve tissue perfusion. METHODS: This was a prospective, randomized, parallel design, single-blind, single-center pilot study. Patients undergoing elective open gynecological surgery requiring a direct arterial line were included. The patients were randomly allocated to two groups. The intervention group received hemodynamic management using the trend of the PI and PPV in an effort to improve tissue perfusion. The control group received hemodynamic management at the discretion of the anesthesia care provider. The primary outcome was the peak lactate level during surgery. The secondary outcomes were the duration of hypotension, intraoperative fluid balance, intraoperative urine output, and postoperative complication rate. Statistical analysis was performed using Student's t test and Fisher's exact test. A P value of < 0.05 was considered statistically significant. RESULTS: Although the intervention significantly decreased the duration of hypotension and intraoperative fluid balance, the peak lactate level was not different between the intervention group and the control group. Intraoperative urine output and postoperative complication rate were not different between the groups. CONCLUSION: Hemodynamic management using the trend of the PI and PPV does not improve tissue perfusion in patients undergoing open gynecological surgery. TRIAL REGISTRATION: This trial was prospectively registered on a publicly accessible database (UMIN Clinical Trials Registry ID: UMIN 000026957. Registered 12 April 2017, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000030916 ).

A case of nephrotic syndrome showing contemporary presence of apolipoprotein E2 homozygote glomerulopathy and membranous nephropathy-like findings modified by apolipoprotein E Toyonaka.

A 79-year-old man was admitted to our hospital for proteinuria due to nephrotic syndrome. Renal biopsy revealed focal sclerosis and foam cell infiltration in the glomerulus. In addition, electron microscopic findings (EM) revealed peculiar electron-dense deposits (EDDs) in both sides of the glomerular basement membrane. Although subepithelial deposits had spike formation highly resembling those seen in membranous nephropathy (MN), immunoglobulins and complements were not identified by immunofluorescence study, and microbubbles appeared in high magnification of EM different from the immune disease. The analysis of apolipoprotein (Apo) E showed an elevated concentration of plasma ApoE. The phenotype, genotype, and DNA sequence studies revealed homozygous ApoE2/2 and a novel missense mutation called ApoE Toyonaka (Ser197Cys). This case may confirm the independent responsibility of ApoE2/2 and ApoE Toyonaka for ApoE2 homozygote glomerulopathy and MN-like EDD findings, respectively.

Focal segmental glomerulosclerosis with heterozygous apolipoprotein E5 (Glu3Lys).

Apolipoprotein (apo) E5 is a rare apoE isoform. The apoE5 (Glu3Lys) variant, which is caused by the substitution of lysine with glutamic acid at codon 3, has a relative frequency of 0.1% in Japan. Previous studies have reported that apoE5 (Glu3Lys) is associated with hyperlipidemia and cardiovascular diseases, but this isoform has higher LDL receptor-binding activity than that of normal apoE3. Nephropathy associated with apoE5 (Glu3Lys) alone has not yet been reported. We present a case of a 51-year-old man with nephrotic syndrome. On renal biopsy, three glomeruli showed segmental sclerosis with hypertrophy of podocytes and intracapillary marked infiltration of intraglomerular foam cells. These findings were compatible with focal segmental glomerulosclerosis (FSGS). The patient had mild diabetes mellitus and monoclonal gammopathy of undetermined significance, but there were no specific findings of nephrolopathy related to these diseases. Various factors are involved in the pathogenesis of FSGS, including dyslipidemia and apoE activity. Our findings suggest that abnormal lipid metabolism by ApoE5 (Glu3Lys) is involved in the onset of FSGS.

Phenylephrine does not improve oxygenation during one-lung ventilation: A randomized, double-blind, cross-over study.

BACKGROUND: Phenylephrine is an α1 adrenergic receptor agonist that causes pulmonary vasoconstriction, and so may effectively enhance hypoxic pulmonary vasoconstriction (HPV). However, there is little evidence that phenylephrine augments HPV in clinical situations. This study aimed to evaluate the clinical effects of phenylephrine infusion on oxygenation during one-lung ventilation (OLV) in patients undergoing thoracic surgery. METHODS: This was a prospective, randomized, double-blind, cross-over study. Included patients were those undergoing elective thoracic surgery in the lateral decubitus position with OLV. Patients were randomly allocated to two groups. The N-P group initially had OLV with normal saline infusion for 30 minutes; after a 10 minute interval, OLV was then maintained with phenylephrine infusion for 30 minutes. The P-N group had the drug-infusion in the reverse order. The primary outcome was arterial partial pressure of oxygen. Secondary outcomes were mean arterial pressure, heart rate, pulse pressure variation, perfusion index, and difference between bladder and skin temperature. Statistical analysis was performed using the student t-test, Fisher's exact test, and ANOVA for Cross-over design. P < 0.05 was considered statistically significant. RESULTS: Twenty-nine patients were analyzed. Although phenylephrine infusion significantly increased mean arterial pressure (P < 0.001), arterial partial pressure of oxygen did not differ between the two timepoints (P = 0.19). There was no carryover effect in arterial partial pressure of oxygen (P = 0.14). Phenylephrine infusion significantly decreased heart rate (P = 0.02) and pulse pressure variation (P < 0.001). CONCLUSIONS: Phenylephrine infusion did not improve oxygenation during OLV. The present results indicate that phenylephrine does not have clinically meaningful effects on HPV. TRIAL REGISTRATION: University Hospital Medical Information Network 000024317.