Current diagnostic methods do not sufficiently identify disease-causing pathogens in severe infectious diseasecases. Prompt identification of causative microorganisms would improve the disease outcome because of antimicrobial treatment optimization. Next-generation sequencing (NGS) is a culture-free method that analyzes theentire microbial community within a sample. Metagenomic sequencing allows us to comprehensively and quantitatively obtain the genes in all organisms present in a clinical sample. Previous studies have attempted to identifypathogens using NGS in various infectious diseases; however, there are currently no established standard protocols to identify causative microorganisms. To establish the standard NGS methods for infectious diseases, studieshave been conducted for severe infectious diseases in our laboratory: acute encephalitis and encephalopathy,acute liver failure, acute myocarditis, blood stream infection and febrile neutropenia under immunocompromisedconditions, and respiratory failure. NGS has advantages over current diagnostic methods in identifying causativepathogens in patients with severe infectious diseases. The routine diagnostic workflow using NGS is expected tobe introduced in clinical settings. NGS can potentially be used to comprehensively analyze drug resistance mutations. Because a number of drug resistance mutations have been reported in patients with cytomegalovirus (CMV)infections treated with ganciclovir, full-length antiviral gene mutation analysis was conducted in congenital CMVinfections. Moreover, NGS can reveal the background microbiome in clinical samples of infectious diseases. Recently, we investigated neonatal respiratory distress-associated microorganisms from microbial genes found inplasma and gastric fluid and assessed their relationship with clinical findings. Because NGS is a comprehensiveanalysis, potential solutions, excluding identifying causative pathogens, are expected to be found.

Hemophilia A is an X-linked inherited bleeding disorder caused by a deficiency of coagulation factor VIII(FVIII) that occurs in approximately 1 in 5,000 male births. Patients with plasma factor activity levels < 1% areclassified as having severe hemophilia. To prevent recurrent joint bleeding, which leads to QOL loss due to severearthropathy, patients need to receive regular intravenous infusions (prophylaxis) of FVIII products. However,there are many concerns regarding 1) the requirement of 2–3 times/week venipuncture for intravenous infusion, 2)frequent visits to the hospital (2–3 times/week in childhood), and 3) one-third of patients with severe hemophiliaA developing anti-FVIII neutralizing alloantibodies (inhibitors) toward the infused factor. Given this, patients andtheir caregivers encounter not only physical stress but also mental and social stress. To resolve these problems,prophylaxis with subcutaneous long-acting nonfactor products that improve in vivo thrombin generation is nowsuccessfully employed in hemophilia patients. These nonfactor products caused a paradigm shift in the treatmentand management of hemophilia. The novel agent emicizumab (Hemlibra®) is a recombinant humanized, bispecificmonoclonal antibody that simultaneously binds to activated factor IX and factor X, thereby mimicking the cofactor function of activated FVIII. Emicizumab has been shown to be safe and effective for the prevention of bleedsin patients with severe hemophilia A, both with and without inhibitors, but it has no indication in hemophilia B.One time/2 or 4 weeks administration was required for maintenance therapy. These benefits contributed by thelong half-life and subcutaneous administration make emicizumab an attractive therapeutic option for prophylaxisin infants with severe hemophilia; however, clinical data to inform treatment decisions in infants are almost absent. As the QOL of hemophilia patients and their caregivers is improved by emicizumab administration, emicizumab might be changed as a mainstream treatment for severe hemophilia in all patients, including infants.

Free-electron lasers at Kyoto University and Nihon University were used as mid-infrared (IR) irradiation stimuli for crayfish compound eyes, and two corneal reactions were detected as the amplitude function of electroretinograms and were identified as a fast reaction and a late reaction. This fast reaction is a new discovery. The spectralsensitivities of the two corneal reactions were measured with an electrophysiological technique at eight selectedmid-IR wavelengths in 2 µm steps ranging from 4 to 18 µm. The wavelength at which maximum sensitivity wasreached was 12–14 µm for the fast reaction and 10–12 µm for the late reaction. In addition, adaptation (attenuationand restoration) of the late reaction to repeated mid-IR stimuli was observed.

BACKGROUNDː Axial postural deformities are frequent and disabling complications of Parkinson’s disease(PD). Although several studies have addressed the effects of deep brain stimulation (DBS) on the improvement ofpostural deformities in PD, there is little detailed information about it. In this paper, we report a prospective observational study evaluating the radiological changes in postural deformities after subthalamic nucleus (STN)-DBSin PD patients.METHODSː Of the 53 patients participating in the present study, 48 were completely followed up prospectivelyfor 12 months after surgery. We assessed the coronal Cobb angulation representing scoliosis, the thoracic andlumbar sagittal Cobb angulation representing thoracic kyphosis and lumbar lordosis, and forward tilt angulation.Anteroposterior and lateral X-rays of the whole spine in the standing position were taken preoperatively and at 6and 12 months postoperatively.RESULTSː The number of PD patients with scoliosis defined as over 10 degrees in terms of the coronal Cobbangles was decreased after STN-DBS, 25/48 (52.1%) at 6 months and 23/48 (47.9%) at 12 months, while preoperatively, 30/48 (62.5%) patients had Cobb angles of over 10. The mean coronal Cobb angle was significantly improved after DBS (14.2 ± 12.1 preoperatively, 12.6 ± 12.6 at 6 months after DBS, and 11.4 ± 11.1 at 12 monthsafter DBS). On the other hand, there was no statistically significant improvement in thoracic kyphosis angulation,lumbar lordosis angulation, and forward tilt angulation after STN-DBS.CONCLUSIONSː The coronal Cobb angles indicated that scoliosis was significantly improved after STN-DBS.

We report two cases of inguinal hernia difficult to diagnose hernia classification.Case 1: The patient was a man in his 70 s who presented to our hospital because of a 4 cm bulge on the cephalicside of the right inguinal ligament. Preoperative computed tomography (CT) revealed prolapse of the small intestine into the right groin, which was diagnosed as an M3-type inguinal hernia. He underwent the transabdominalpreperitoneal approach (TAPP). On examination of the abdominal cavity, coexisting M3/F2 inguinal hernias werediagnosed. A retrospective CT revealed a femoral hernia in the coronal section image. Case 2: The patient was awoman in her 80 s who presented with a 6 cm bulge on the cephalic side of the right inguinal ligament. Based onphysical examination and CT findings, she was diagnosed with coexisting L2/F1 hernias and underwent TAPPhernia repair. Multiplanar reconstruction-CT is useful for hernia classification. TAPP hernia repair is a techniquecapable of accurately diagnosing and reliably repairing coexisting inguinal hernias.

Methotrexate (MTX)-associated lymphoproliferative disorder (MTX-LPD) is a known adverse event of MTXand rarely originates in the central nervous system (CNS). There are few case reports related to CNS LPDs; therefore, an effective treatment has not been established. We report a case of primary CNS MTX-LPD treated witha new combination chemotherapy consisting of rituximab, procarbazine, methotrexate, and vincristine (R-MPVtherapy). A 56-year-old woman presented with chief complaints of headache, memory disturbance, and gait disturbance. She had taken MTX for rheumatoid arthritis for 25 years. Magnetic resonance imaging demonstrated tumorlesions in the left frontal and occipital lobes. The tumor was removed via craniotomy and diagnosed as MTXLPD. MTX therapy was discontinued, but no tumor regression was observed. Although R-MPV therapy wasstarted, no obvious regression was obtained. The patient died after 4 courses of R-MPV therapy. If chemotherapyachieves limited effects for patients with CNS MTX-LPD, early introduction of radiotherapy or change to otherchemotherapy should be considered.

A 26-year-old man was admitted with a chief complaint of melena. An abdominal CT scan revealed a 40 mmdiameter tumor in the pancreatic head, while upper and lower endoscopy did not reveal the bleeding origin.Contrast-enhanced CT showed a well-enhanced mass located on the ventral side of the pancreas. As endoscopicultrasound confirmed rich arterial blood flow around the mass, fine needle biopsy could not be performed. Underthe tentative diagnosis of gastrointestinal stromal tumor (GIST) or neuroendocrine tumor (NET), a pancreatoduodenectomy was performed. An elastic-hard 45 mm tumor was located at the ventral side of the pancreatic headand was compressed to the duodenum. Pathological examination revealed that round to oval or spindle-shapedatypical cells were growing in the stroma. Finally, an immunobiological study revealed a NET in the pancreas.Pancreatic NETs are relatively rare, accounting for approximately 2% of pancreatic tumors.