Point mutations in the steroid-binding domain of the androgen receptor gene of five Japanese patients with androgen insensitivity syndrome.

We analyzed the androgen receptor (AR) gene in five Japanese patients diagnosed with androgen insensitivity syndrome (AIS). All AR genes from the five patients had single-nucleotide substitutions, which introduced a premature termination codon in three patients (Gln640, Arg752, and Gln640 and Trp751), and a single amino acid substitution in two patients (Arg831 to Gln, and Leu812 to Phe). All the mutations occurred in the steroid-binding domain, comprising exons D through G. The three patients with the premature termination codon(s) and the one patient with Arg831Gln were clinically diagnosed as having complete AIS, while the patient with Leu812Phe had a partial form of AIS. Pubic skin fibroblasts from four of the five patients did not show detectable androgen binding. These data on mutations that have not been reported previously, provide valuable information for the further characterization of structural and functional relationships in the steroid-binding domain of the AR protein.     

Complete hydatidiform mole with coexisting dichorionic diamniotic twins following testicular sperm extraction and intracytoplasmic sperm injection

We present the first report of complete hydatidiform mole (HM) with coexisting dichorionic diamniotic twins. This pregnancy was achieved after testicular sperm extraction and intracytoplasmic sperm injection (ICSI) for azoospermia in the woman's husband. Standard in vitro fertilization may cause multisperm fertilization and increase triploid partial HM and complete HM, which arise from dispermic fertilization. In contrast, ICSI can avoid multisperm fertilization. In our case, paternal isodisomy in the molar tissue was confirmed by microsatellite analysis suggesting that it resulted from duplication of a haploid paternal genome following monospermic fertilization of an inactivated oocyte or from monospermic fertilization of an inactivated oocyte with a diploid sperm. Although the patient was eager to continue the pregnancy, the size of the HM component increased rapidly and termination of the pregnancy was required for pre-eclampsia-like symptoms at 15 weeks of gestation. After the operation, chemotherapy was initiated for persistent trophoblastic disease.     

Update on classification,diagnosis, and management of immunoglobulin G4-related disease

Immunoglobulin G4-related disease (IgG4-RD) is a newly recognized chronic fibro-inflammatory autoimmune disease, and its recognition has been constantly increasing worldwide over the last few years. A correct and timely recognition, as well as appropriate intervention, is crucial for the treatment of IgG4-RD. For certain subtypes of IgG4-RD, organ-specific criteria are formulated to make the diagnosis more accurate. New biomarkers have emerged in the recent years to aid the disease diagnosis, it...     

Mutations of syntaxin 11 and SNAP23 genes as causes of familial hemophagocytic lymphohistiocytosis were not found in Japanese people

Although mutations of perforin, MUNC13-4 and syntaxin 11 genes have been found in children with familial hemophagocytic lymphohistiocytosis (FHL), the incidence of each genetic subtype varies in different ethnic groups. We evaluated mutations of syntaxin 11 and SNAP23 genes in 30 Japanese FHL patients. The patients had no mutations and 10% had one polymorphism (146G>A) of syntaxin 11, while no mutation of SNAP23 was observed. Our results indicate that aberrations in the SNARE system may not cause FHL in Japanese families.     

Pks-positive Escherichia coli in tumor tissue and surrounding normal mucosal tissue of colorectal cancer patients

A significant association exists between the gut microbiome and colorectal carcinogenesis, as well as cancer progression. It has been reported that Escherichia coli (E. coli) containing polyketide synthetase (pks) island contribute to colorectal carcinogenesis by producing colibactin, a polyketide-peptide genotoxin. However, the functions of pks⁺ E. coli in initiation, proliferation, and metastasis of colorectal cancer (CRC) remain unclear. We investigated the clinical significance of pks⁺ E. coli to clarify its functions in CRC. This study included 413 patients with CRC. Pks⁺ E. coli of tumor tissue and normal mucosal tissue were quantified using droplet digital PCR. Pks⁺ E. coli was more abundant in Stages 0–I tumor tissue than in normal mucosal tissue or in Stages II–IV tumor tissue. High abundance of pks⁺ E. coli in tumor tissue was significantly associated with shallower tumor depth (hazard ratio [HR] = 5.0, 95% confidence interval [CI] = 2.3–11.3, p < 0.001) and absence of lymph node metastasis (HR = 3.0, 95% CI = 1.8–5.1, p < 0.001) in multivariable logistic analyses. Pks⁺ E. coli-low and -negative groups were significantly associated with shorter CRC-specific survival (HR = 6.4, 95% CI = 1.7–25.6, p = 0.005) and shorter relapse-free survival (HR = 3.1, 95% CI = 1.3–7.3, p = 0.01) compared to the pks⁺ E. coli-high group. Pks⁺ E. coli was abundant in Stages 0–I CRC and associated with CRC prognosis. These results suggest that pks⁺ E. coli might contribute to carcinogenesis of CRC but might not be associated with tumor progression.     

Surgical outcomes of acute type A aortic dissection in patients undergoing cardiopulmonary resuscitation

ObjectivesThe surgical indications for acute type A aortic dissection (AAAD) in patients in cardiopulmonary arrest remain controversial. Outcomes of AAAD for patients who underwent cardiopulmonary resuscitation (CPR) were evaluated.MethodsBetween 2004 and 2018, of the 519 patients who underwent AAAD repair, 34 (6.6%) required CPR before or on starting AAAD repair. The patients were divided into 2 groups, survivors (n = 13) and nonsurvivors (n = 21), to compare the early operative outcomes, including mortality and neurological events.ResultsThe major cause of cardiovascular collapse requiring CPR was aortic rupture/cardiac tamponade (n = 21 [61.8%]), followed by coronary malperfusion (n = 12 [35.3%]) and acute aortic valve regurgitation (n = 3 [8.8%]). There were 3 (23.1%) patients in the survivors group and 11 (52.4%) in the nonsurvivors group who required ongoing CPR at the beginning of AAAD repair (P = .039). Of these patients, 1 survivor and 6 nonsurvivors could not achieve return of spontaneous circulation after pericardiotomy (P = .045). Although the duration from onset or arrival to the operating room was similar (P = .35 and P = .49, respectively), overall duration of CPR was shorter in survivors (10 minutes [range, 7.5-16 minutes] vs 16.5 minutes [range, 15-20 minutes]; P = .044). All survivors without any neurological deficits showed return of spontaneous circulation after pericardiotomy. Multivariate regression modeling showed that CPR duration >15 minutes was a significant risk factor for in-hospital mortality (P = .0040).ConclusionsCPR duration beyond 15 minutes may be a contraindication for AAAD repair. Moreover, we should reconsider surgery for patients who cannot achieve return of spontaneous circulation after pericardiotomy.     

Blood sugar control reverses the increase in urinary excretion of prostaglandin D synthase in diabetic patients

BACKGROUND/AIMS: We investigated basal levels of serum and urinary lipocalin-type prostaglandin D synthase/beta-trace (L-PGDS) in type-2 diabetic patients and explored whether glycemic control affects L-PGDS status in another 55 diabetic inpatients with normoalbuminuria. METHODS: Fifty-five type-2 diabetic outpatients (HbA1c, 9.14 +/- 0.20%; creatinine (Cr), 85.1 +/- 2.4 micromol/l), and 55 age-matched healthy control subjects were recruited. Serum and urinary levels of L-PGDS were determined with respect to the stage of diabetic nephropathy. The L-PGDS was localized by immunohistochemistry. RESULTS: The urinary L-PGDS index increased in diabetic patients, compared with the controls (234.8 +/- 27.4 vs. 73.8 +/- 7.8 microg/mmol Cr, p < 0.001). Even in normoalbuminuric patients as well as in microalbuminuric patients, urinary L-PGDS indexes were higher than the controls (166.0 +/- 21.1, p < 0.0001 and 338.6 +/- 62.5 microg/mmol Cr, p < 0.0001, respectively), although the serum L-PGDS level was equal to that in the control subjects. Multiple regression analysis revealed that the urinary L-PGDS index was predicted solely by glucose levels and type-IV collagen index, whereas the serum L-PGDS was determined mainly by age and serum Cr. Glycemic control reduced the urinary L-PGDS index towards the normal range in diabetic patients with normoalbuminuria (172.3 +/- 6.6 vs. 118.1 +/- 2.6 (SE) microg/mmol Cr, p < 0.0001). Immunohistochemistry showed that L-PGDS was uniquely present in the renal tubules in diabetes while in nondiabetics, L-PGDS occurred solely in the peritubular interstitium, not in the tubular cells. CONCLUSION: Inadequate glycemic control is responsible for urinary L-PGDS excretion in the diabetic patients. Urinary L-PGDS is useful to predict subclinical renal injury associated with type-2 diabetes.     

Bone anatomy and rotational alignment in total knee arthroplasty

The purpose of the current study was to investigate the bone anatomy in determining the rotational alignment in total knee arthroplasty using computed tomography. Axial images of 109 knees in 83 patients with varus osteoarthritis who had total knee arthroplasty were analyzed. On the images of the distal femur and the proximal tibia, a baseline for the anteroposterior axis of each component was drawn based on the epicondylar axis for the femur and the medial (1/3) of the tibial tuberosity for the tibia. The angle between these two lines was analyzed as the rotational mismatch between the components when they were aligned to the anatomic landmarks of each bone. Fifty-four knees (49.5%) had an angle of 5 degrees or greater and 13 knees (11.9%) had an angle of 10 degrees or greater. There was a tendency to align the tibial component in external rotation relative to the femoral component. The results indicated that the landmarks of each bone were the intrinsic cause of the rotational mismatch in knees with varus osteoarthritis. Surgeons doing total knee arthroplasties should be aware of this and check the rotational mismatch between the components. When it is present, the tibial component should be realigned to match the femoral component rotation to minimize problems caused by the mismatch.