Contrasting seasonality of the incidence of incisional surgical site infection after general and gastroenterological surgery: an analysis of 8436 patients in a single institute.

BACKGROUND: While seasonality of hospital-acquired infections, including incisional SSI after orthopaedic surgery, is recognized, the seasonality of incisional SSI after general and gastroenterological surgeries remains unclear. AIM: To analyse the seasonality and risk factors of incisional SSI after general and gastroenterological surgeries. METHODS: This was a retrospective, single-institute, observational study using univariate and multivariate analyses. The evaluated variables included age, sex, surgical approach, surgical urgency, operation time, wound classification, and the American Society of Anesthesiologists physical status (ASA-PS). FINDINGS: A total of 8436 patients were enrolled. General surgeries (N = 2241) showed a pronounced SSI incidence in summer (3.9%; odds ratio (OR): 1.87; 95% confidence interval (CI): 1.05-3.27; P = 0.025) compared to other seasons (2.1%). Conversely, gastroenterological surgeries (N = 6195) showed a higher incidence in winter (8.3%; OR: 1.38; 95% CI: 1.10-1.73; P = 0.005) than in other seasons (6.1%). Summer for general surgery (OR: 1.90; 95% CI: 1.12-3.24; P = 0.018) and winter for gastroenterological surgery (1.46; 1.17-1.82; P = 0.001) emerged as independent risk factors for incisional SSI. Open surgery (OR: 2.72; 95% CI: 1.73-4.29; P < 0.001) and an ASA-PS score ≥3 (1.64; 1.08-2.50; P = 0.021) were independent risk factors for incisional SSI in patients undergoing gastroenterological surgery during winter. CONCLUSION: Seasonality exists in the incisional SSI incidence following general and gastroenterological surgeries. Recognizing these trends may help enhance preventive strategies, highlighting the elevated risk in summer for general surgery and in winter for gastroenterological surgery.

Identification of ABCG2 as an Exporter of Uremic Toxin Indoxyl Sulfate in Mice and as a Crucial Factor Influencing CKD Progression.

Chronic kidney disease (CKD) patients accumulate uremic toxins in the body, potentially require dialysis, and can eventually develop cardiovascular disease. CKD incidence has increased worldwide, and preventing CKD progression is one of the most important goals in clinical treatment. In this study, we conducted a series of in vitro and in vivo experiments and employed a metabolomics approach to investigate CKD. Our results demonstrated that ATP-binding cassette transporter subfamily G member 2 (ABCG2) is a major transporter of the uremic toxin indoxyl sulfate. ABCG2 regulates the pathophysiological excretion of indoxyl sulfate and strongly affects CKD survival rates. Our study is the first to report ABCG2 as a physiological exporter of indoxyl sulfate and identify ABCG2 as a crucial factor influencing CKD progression, consistent with the observed association between ABCG2 function and age of dialysis onset in humans. The above findings provided valuable knowledge on the complex regulatory mechanisms that regulate the transport of uremic toxins in our body and serve as a basis for preventive and individualized treatment of CKD.

Recurrent peritoneal inclusion cysts successfully treated with oral contraceptives: a report of two cases.

OBJECTIVE: To examine whether conservative treatment with oral contraceptives is effective in the shrinkage of a peritoneal inclusion cyst (PIC). This is a case report of two patients with a PIC that developed after gynecological surgery. CASES: Both cases were suspected of a PIC based on the medical history, laboratory data, and image findings. It was difficult in differentiate a PIC from an ovarian tumor. Surgery was chosen at first. However, PICs in both cases recurred after surgery and were treated with oral contraceptives as a conservative treatment. PICs shrank after the treatment of oral contraceptives in both cases. CONCLUSION: Due to the high rate of recurrence following surgery, conservative treatment is recommended to treat PICs. Hormone therapy using oral contraceptives seems to have some therapeutic benefit for the PICs.

Identification of ABCG2 dysfunction as a major factor contributing to gout.

The ATP-binding cassette, subfamily G, member 2 gene ABCG2/BCRP locates in a gout-susceptibility locus (MIM 138900) on chromosome 4q. Recent genome-wide association studies also showed that the ABCG2 gene relates to serum uric acid levels and gout. Since ABCG2 is also known as a transporter of nucleotide analogs that are structurally similar to urate, and is an exporter that has common polymorphic reduced functionality variants, ABCG2 could be a urate secretion transporter and a gene causing gout. To find candidate mutations in ABCG2, we performed a mutation analysis of the ABCG2 gene in 90 Japanese patients with hyperuricemia and found six non-synonymous mutations. Among the variants, ATP-dependent urate transport was reduced or eliminated in five variants, and two out of the five variants (Q126X and Q141K) were frequently detected in patients. Haplotype frequency analysis revealed that there is no simultaneous presence of Q126X and Q141K in one haplotype. As Q126X and Q141K are a nonfunctional and half-functional haplotype, respectively, their genotype combinations are divided into four estimated functional groups. The association study with 161 male gout patients and 865 male controls showed that all of those who had dysfunctional ABCG2 had an increased risk of gout, and that a remarkable risk was observed in those with ≤1/4 function (OR, 25.8; 95% CI, 10.3-64.6; p = 3.39 × 10(-21)). In 2,150 Japanese individuals, the frequency of those with dysfunctional ABCG2 was more than 50%. Our function-based clinicogenetic analysis identified the combinations of dysfunctional variants of ABCG2 as a major contributing factor in Japanese patients with gout.

Two cases of nephrotic syndrome (NS)-induced acute kidney injury (AKI) associated with renal hypouricemia.

Renal hypouricemia is a clinical disorder attributed to an increased renal urate excretion rate and is well known to involve a high risk of urolithiasis and exercise-induced acute kidney injury (AKI). This report concerns two interesting cases of nephrotic syndrome (NS)-induced AKI associated with renal hypouricemia. A 64-year-old female (Case 1) and a 37-year-old male (Case 2) were hospitalized because of AKI (serum creatinine: 2.07 mg/dl and 3.3 mg/dl, respectively), oliguria and NS. They were treated with prednisolone and temporary hemodialysis. Renal function improved, but hypouricemia persisted during hospitalization. Histological findings in both cases led to a diagnosis of minimal change nephrotic syndrome and identification of the diuretic phase of tubulointerstitial damage because of findings such as acute tubular necrosis. Furthermore, distal tubules of Case 2 showed an amorphous mass, possibly a uric acid crystal. Analysis of the two cases with the URAT1 gene, encoded by SLC22A12, found a homozygous mutation in exon 4 (W258stop) of each one. Our cases show that patients with renal hypouricemia may be susceptible to AKI without involvement of exercise if they possess some facilitators. Renal hypouricemic patients should therefore be carefully examined for all complications from renal hypouricemia because of high risk of AKI.

Establishment and analysis of SLC22A12 (URAT1) knockout mouse.

In order to elucidate the mechanisms of post-exercise acute renal failure, one of the complications of hereditary renal hypouricemia, we have targeted the mouse Slc22a12 gene by the exchange of exons 1-4 with pMC1neo-polyA. The knockout mice revealed no gross anomalies. The concentration ratio of urinary urate/creatinine of the knockout mice was significantly higher than that of wildtype mice, indicating an attenuated renal reabsorption of urate. The plasma levels of urate were around 11 muM and were similar among the genotypes. Although the fractional excretion of urate of knockout mice was tend to higher than that of wildtype mice, the urate reabsorption ability remained in the kidney of knockout mice, indicating a urate reabsorptive transporter other than Urat1.

Age and origin of the G774A mutation in SLC22A12 causing renal hypouricemia in Japanese.

Renal hypouricemia is an inherited disorder characterized by impaired tubular uric acid transport. Impairment of the function of URAT1, the main transporter for the reabsorption of uric acid at the apical membrane of the renal tubules, causes renal hypouricemia. The G774A mutation in the SLC22A12 gene encoding URAT1 predominates in Japanese renal hypouricemia. From data on linkage disequilibrium between the G774 locus and the 13 markers flanking it (12 single nucleotide polymorphisms and 1 dinucleotide insertion/deletion locus), we here estimate the age of this mutation at approximately 6820 years [95% confidence interval (CI) 1860-11,760 years; median = 2460 years]. This indicates that the origin of the G774A mutation dates back from between the time when the Jomon people predominated in Japan and the time when the Yayoi people started to migrate to Japan from the Korean peninsula. These data are consistent with a recent finding that this G774A mutation was also predominant in Koreans with hypouricemia and indicate that the mutation originated on the Asian continent. Thus, this mutation found in Japanese patients was originally brought by immigrant(s) from the continent and thereafter expanded in the Japanese population either by founder effects or by genetic drift (or both).

Serum uric acid and renal prognosis in patients with IgA nephropathy.

BACKGROUND/AIMS: This study was designed to elucidate the clinical significance of serum uric acid (SUA) and the relationship between hyperuricemia and renal prognosis in IgA nephropathy. METHODS: The correlation between SUA and other clinical parameters were examined in 748 IgA nephropathy patients (432 males and 316 females). Among these patients, 226 (144 males and 82 females) who were followed for more than 5 years were examined for the relationship between hyperuricemia and renal prognosis. RESULTS: In IgA nephropathy, SUA correlated negatively with creatinine clearance (Ccr), and positively with urinary protein and tubulointerstitial damage. SUA was higher in patients with hypertension or diffuse proliferative glomerulonephritis. Hyperuricemia was a risk factor for renal prognosis, both in terms of serum creatinine (p = 0.0025) and Ccr (p = 0.0057). In 56 patients with normal Ccr at renal biopsy, the change of Ccr after more than 8 years was -22.3 +/- 20.8% in 13 patients with hyperuricemia, compared with +2.6 +/- 39.4% in 43 patients without hyperuricemia (p = 0.0238). Hyperuricemia was related independently to deterioration of Ccr (p = 0.0461). CONCLUSION: Hyperuricemia in IgA nephropathy is derived from both glomerular and tubulointerstitial damage, and correlated with hypertension. Hyperuricemia is a risk factor for renal prognosis in IgA nephropathy.

Characterization of a palytoxin-induced non-selective cation channel in mouse megakaryocytes.

We used the whole-cell clamp and fura-2 techniques to study the membrane current and intracellular Ca2+ concentration ([Ca2+]i) changes of mouse megakaryocytes in response to palytoxin (PTX), a highly potent marine toxin. At a holding potential of -60 mV, PTX induced a sustained inward current in a dose-dependent manner. The reversal potentials measured in the presence of various extracellular major cations indicated that the PTX-induced channel had a non-selective permeability to alkali metal ions. Although elimination of intracellular Ca2+ had no effect on the PTX-induced current, removal of external Ca2+ inhibited the current activation. During the sustained phase of the PTX-induced current, treatment with ADP activated an additional current. Pretreatment with ouabain, an inhibitor of Na+-K+-ATPase, suppressed the PTX-induced current. During the stable phase of the PTX-induced current, challenge with NiCl2 (5 mM) or 2,4-dichlorobenzamil (DCB, 25 microM), a non-selective cation channel blocker, partially reversed the current. Simultaneous measurement of the membrane current and [Ca2+]i showed that PTX induced the current response without increasing the [Ca2+]i. Taken together, these results indicate that PTX induces a non-selective cation channel in mouse megakaryocytes. This channel is distinct from the ADP-operated channel and is sensitive to ouabain, NiCl2 and DCB.

Partial deficiency of hypoxanthine-guanine phosphoribosyltransferase manifesting as acute renal damage.

A 32-year-old man who had had frequent gouty arthritis over the past 17 years, was admitted for acute renal failure. Acute renal failure was improved rapidly after medication was resumed and the patient was sufficiently hydrated. The hypoxanthine-guanine phosphoribosyltransferase (HPRT) activity in the patient had been reduced to about 30% of the normal control. Therefore we considered that this patient suffered from a partial deficiency of HPRT. A point mutation of HPRT gene 68G (guanine) to T (thymine) was detected. This is a mutation that has not been previously reported. Familial analysis indicated that his mother and sister were heterozygotes.

Two siblings with classical xanthinuria type 1: significance of allopurinol loading test.

Two brothers with classical xanthinuria who lacked xanthine dehydrogenase activity were encountered. Their hypouricemia was caused by underproduction of uric acid. In their duodenal mucosa, no xanthine dehydrogenase (oxidase) activity was detected. The patients had no symptoms except for duodenal ulcer in one case. The conversion of allopurinol to oxipurinol during an allopurinol loading test for determining the type of classical xanthinuria revealed that the patients had classical type 1 xanthinuria, because aldehyde oxidase activity was present. Furthermore, the allopurinol loading test was conducted to determine the optimal examination times and specimens required for this test.

[Hyperuricemia and the kidney].

The risk for renal insufficiency by uric acid precipitation in medulla of kidney correlates with the degree of uric acid supersaturation in the urine, depending on uric acid concentration and urinary pH. The patients with gout or hyperuricemia have sometimes acidic urine and increased uric acid excretion. Accordingly, these patients frequently accompany by renal insufficiency. Improvement of hyperuricosuria, increasing of urine volume, and alkalinization of urine to pH6 6.5, are effective for the prevention from renal insufficiency. Acute renal failure related to hyperuricemia, can also occured secondary to cell lysis. Tumor lysis syndrome is a critical illness characterized by massive tumor cell death leading to severe hyperuricemia, hyperphosphatemia, hypocalcemia, and acute renal failure after starting chemotherapy to cancers, especially lymphoproliferative malignancies. Administration of allopurinol 500-600 mg and adequate hydration and alkalinization of urine are advocated to prevent acute renal failure. Intensive care with hemodialysis is often required to treat renal failure, because renal failure is reversible in most cases.

[Metabolic disorder of purine nucleotide in patients with renal disease].

The serum levels of uric acid, hypoxanthine and xanthine tended to increase with the decrease of renal function. This mechanism was thought to be the decreased excretion of these materials from the kidney. More than ninety percent of the patients with renal insufficiency (Ccr < or = 30 ml/min) showed hyperuricemia. In general, the gouty arthritis was reported to be uncommon in the patients with secondary hyperuricemia due to renal insufficiency. However, the frequency of gouty arthritis was reported to be high in the patients with polycystic disease and lead nephropathy. The therapeutic standard for secondary hyperuricemia with renal insufficiency was not established. Allopurinol is the drug of choice for controlling hyperuricemia due to renal insufficiency in many cases. In renal insufficiency, the drug must be used cautiously and in reduced dosage because increased serum concentration of oxipurinol, active metabolite of allopurinol, may induce severe side effect.

A rare case of idiopathic hypoparathyroidism with varied neurological manifestations.

A 47-year-old man was admitted for evaluation of unsteady gait, postural instability, and dysarthria. On admission, neurological examinations revealed cerebellar ataxia, extrapyramidal signs including parkinsonism and positive Trousseau's sign. Laboratory findings revealed severe hypocalcemia and hyperphosphatemia, and serum intact parathyroid hormone was not detectable. Brain computed tomography revealed severe calcification of basal ganglia and dentate nuclei. He was diagnosed as idiopathic hypoparathyroidism; treatment with 1 alpha (OH) vitamin D3 brought marked improvement of neurological manifestations. We report a rare case of idiopathic hypoparathyroidism presenting with extrapyramidal and cerebellar dysfunction with a review of literature.

Newly discovered familial juvenile gouty nephropathy in a Japanese family.

Our attention was initially called to 2 young Japanese sisters with gout and renal insufficiency, which led to an investigation of members of their family with similar conditions. One sister, a 26-year-old woman who had suffered from polyuria since infancy, suffered from gout and renal insufficiency. Her younger sister also had a history of polyuria, hyperuricemia, and moderately reduced renal function. Their urinary uric acid levels were reduced but purine enzyme activities in the erythrocytes were normal. A renal biopsy specimen from the younger sister showed severe interstitial fibrosis with tubular atrophy. An investigation of the family revealed an autosomal dominant transmission pattern. We believe these are new familial cases of juvenile gouty nephropathy found in a Japanese family.

Pitfalls in fine needle aspiration cytology of breast tumors. A report of two cases.

Two cases of fibroadenoma that were cytologically misdiagnosed as mucous carcinoma are reported. The reason for this misdiagnosis was the presence of mucus in the background of the smears. Cytologically, even if plenty of mucus is present in a smear, careful observation of the content of the mucus is necessary. A group of stromal cells in mucus or of epithelial cells dissociated from mucus suggests fibroadenoma with a mucous change in the fibromatous tissue.

[A study on treatment of hyperuricemia--effects and kinetics of allopurinol and oxipurinol].

In order to study the effects and pharmacokinetics of allopurinol (hereafter abbreviated to allo.) and oxipurinol (hereafter abbreviated to oxi.) six normal human subjects were given a single oral dose of either allo. (300mg) or oxi. (600mg), followed by serial determinations of serum and urinary levels of allo., oxi., uric acid, hypoxanthine (hereafter abbreviated to hx.) and xanthine (hereafter abbreviated x.) over a six-hour period. With a dose of 300mg of allo. or 600mg of oxi., the patterns of serum uric acid were similar. When 300mg of allo. was given, however, a reduction in the serum uric acid level occurred earlier. Additionally, it was found that urinary excretion of oxi. generally paralleled the plasma concentration. Allo. administration resulted in rises in plasma concentration of x., and urinary excretion of x. and hx. Oxi. administration, on the other hand, did not cause significant changes in the plasma content of x. or urinary excretory volume of hx. Only a slight increase was noted in the amount of x. excreted in the urine. When allo. was compared against oxi., pharmacokinetics of oxypurines, especially x. were found to differ markedly. The results suggested that differences in the reaction sites, varied intra- and extra-cellular distributions of allo. and oxi., and different effects on purine biosynthesis contribute to the aforementioned discrepancies.

Malignant hypertension in three siblings.

We encountered three siblings (one female and two males) whose clinical manifestations were consistent with those of malignant hypertension (MH). Renal biopsies were obtained from two of the patients, and an autopsy from the third. The light microscopic findings from all three cases were characterised by marked intimal thickening with concentric layering of collagen and cellular proliferation in the interlobular arteries. Findings, on examination of optic fundi, including retinal haemorrhages, exudates and papilloedema were also consistent with malignant hypertension. The two male patients progressed to develop renal failure. These cases strongly suggest the existence of a rare familial form of primary malignant hypertension.