Human mpox presenting with penile edema and ulcer: A case report.

Human mpox, which has spread worldwide since May 2022, is characterized by symptoms involving the genital area; however, its treatment methods and clinical course are not completely understood. Furthermore, penile swelling in human mpox can be difficult to differentiate from cellulitis and antibiotic use has been reported in such cases. Herein, we report a case of human mpox in Japan with prominent penile swelling and persistent penile ulcers that improved without specific treatment. The patient was a Japanese man in his 20s with a history of having sexual intercourse with men frequently. He visited Tokyo Metropolitan Toshima Hospital because of a fever and rash in the genital area. Physical examination revealed vesicles on the limbs, penile pigmentation, and significant penile swelling and redness. There were no signs of cellulitis and symptomatic treatment was initiated with outpatient follow-up. After 7 days, an improving trend in penile swelling, redness, and pain was observed. However, a partially black skin ulcer with exudate was observed at the left coronal sulcus of the penis. Therefore, the symptomatic treatment was continued. On illness day 28, the penile swelling completely improved; however, the penile ulcer and pain persisted, and the exudate was observed again. By illness day 63, the pain in his anogenital area had disappeared, and the penile skin ulcer had healed. The following observations were noted in this case: (i) human mpox can improve without specific treatment such as tecovirimat administration and (ii) skin lesions in the genital area may change over time.

[Evaluation of Patients with Localized Prostate Cancer in whom Long-Term Successful Androgen Deprivation Therapy was Ceased].

We evaluated the clinical course of patients with localized prostate cancer in whom long-term successful androgen deprivation therapy (ADT) was ceased. Study subjects were 24 patients with stage B prostate cancer who were initially treated with ADT for a median duration of 93 months. The median age at the cessation of ADT was 84 years. The median nadir serum prostate specific antigen (PSA) level was 0.022 ng/ml. The median duration of follow-up from the cessation of ADT was 31 months. During follow-up, five patients showed PSA elevation of ≥2 ng/ml from the nadir. Serum testosterone level was tested in 20 patients, and five showed testosterone recovery ≥0.5 ng/ml. Seven patients died from diseases other than prostate cancer, but there were no deaths caused by prostate cancer. This study demonstrated that long-term successful ADT for localized prostate cancer could be ceased with adequate follow-up evaluation.

[A Case of Castration-Resistant Prostate Cancer after Prostatectomy Treated with Resection of A Solitary Metastatic Site].

A 72-year-old man underwent a bilateral nerve-sparing radical retropubic prostatectomy (RRP) with pelvic lymph node dissection 11 years earlier. His prostate specific antigen (PSA) value at diagnosis was 61.024 ng/ml. Bone scans and computed tomographic (CT) scans showed no metastasis. Pathological findings and stage were adenocarcinoma, Gleason score 4+3, positive surgical margin, pT3b, and no lymph node metastasis. The postoperative PSA nadir was 0.218 ng/ml, and salvage radiotherapy (SRT, total 66 Gy) was performed six months after RRP. However, the PSA value continued to rise after SRT. Therefore, androgen deprivation therapy (ADT) was started 11 months after SRT. Nine years postoperatively, the PSA value showed a continuous rise despite ADT, and prostate cancer was considered to be castration-resistant. Although he was taking enzalutamide, his PSA value rose to 18. 271 ng/ml. Repeated bone scans and CT scans were negative. Eleven years after RRP, the fluoro-2-deoxy-D-glucosepositronemissiontomography (FDG-PET) revealed a nodule lesiondorsal to the left pubic bone. The patient underwent a resection of the lesion. Three months after the resection, his PSA level declined to 0.038 ng/ml, thus ADT was discontinued. Thirteen months after the resection, PSA re-elevation was absent, and follow-up without ADT is ongoing.

[A Case of Emphysematous Pyelonephritis Complicated by Bacterial Endophthalmitis in which Multidisciplinary Therapy Led to Preservation of the Kidney].

A 49-year-old male with untreated diabetes mellitus type 2 experienced eyesight deterioration and general malaise, and was treated for uveitis and orbital cellulitis. Later, he was taken to a local hospital via ambulance for a consciousness disorder and was diagnosed with bilateral infectious endophthalmitis, a right ureteral stone, and emphysematous pyelonephritis. He was then referred to our hospital for further examination and treatment. We immediately initiated intravenous antibiotic therapy with meropenem and glycemic control with continuous subcutaneous insulin infusion, and placed a ureteral and percutaneous drain tube into the right ureter and the emphysema, respectively. We performed a diagnostic and therapeutic vitrectomy on the patient's left eye. Urinary, blood, and vitreous cultures were positive for Klebsiella aerogenes. Abdominal contrast-enhanced computed tomography showed bilaterally comparable renal contrast enhancement. On the 60th hospital day, we performed endoscopic combined intrarenal surgery (ECIRS) and completely removed the urinary stone. Although he lost light sensitivity in his right eye, his left eyesight improved, and his blood glucose level was adequately managed by oral medication. Three months after the surgery, he was discharged from our hospital and he showed no sign of recurrence of the infection at ten months after surgery.

Monitoring Shedding of Five Genotypes of RotaTeq Vaccine Viruses by Genotype-Specific Real-Time Reverse Transcription-PCR Assays.

RotaTeq (RV5) is a widely used live attenuated pentavalent rotavirus (RV) vaccine. Although fecal shedding of RV vaccine strains persists for long time periods, it is unclear how each vaccine strain replicates in intestinal tissue and is excreted in stool. To examine this issue, we established RV5 genotype-specific real-time reverse transcription-PCR (RT-PCR) assays. Five real-time RT-PCR assays were designed for the VP7 gene in genotypes G1, G2, G3, G4, and G6. All assays exhibited excellent linearity, and the detection limit was 1 infectious unit (IU)/reaction for G2, G4, and G6 and 10 IUs/reaction for G1 and G3. No cross-reactivity was observed among G genotypes. The inter- and intra-assay coefficients of variation were less than 3%. The assays were used to examine 129 stool samples collected from eight infants who received RV5. In cases 1 and 2, who received three rounds of vaccination, RV shedding decreased gradually with the number of vaccinations. G1 and G6 shedding appeared to be predominant in comparison to shedding of the other genotypes. Patterns of fecal shedding of the five genotypes of vaccine viruses differed between the eight vaccine recipients. RV5 genotype-specific real-time RT-PCR assays will be useful to study the molecular biology of RV5 replication in infants and experimental animals.

[A Case of Nivolumab-Induced Isolated Adrenocorticotropic Hormone Deficiency Presenting Dyspnea].

A 66-year-old man had undergone multiple treatments for metastatic renal cell carcinoma, including 11 cycles of nivolumab, which was discontinued because of disease progression. About three weeks after discontinuing nivolumab, he reported suffering from worsening of dyspnea. Pulse oximetry showed no desaturation. His cardiovascular and pulmonary functions were normal. His dyspnea slowly worsened with no underlying diagnosis. Two months after symptoms developed, he was diagnosed with isolated adrenocorticotropic hormone deficiency. His dyspnea disappeared soon after receiving hydrocortisone. Nivolumab-induced isolated adrenocorticotropic hormone deficiency may not present with typical symptoms, and can occur even after discontinuing nivolumab. Cortisol levels should be routinely monitored in patients who receive nivolumab.

Pioglitazone suppresses neuronal and muscular degeneration caused by polyglutamine-expanded androgen receptors.

Spinal and bulbar muscular atrophy (SBMA) is a neuromuscular disease caused by the expansion of a CAG repeat in the androgen receptor (AR) gene. Mutant AR has been postulated to alter the expression of genes important for mitochondrial function and induce mitochondrial dysfunction. Here, we show that the expression levels of peroxisome proliferator-activated receptor-γ (PPARγ), a key regulator of mitochondrial biogenesis, were decreased in mouse and cellular models of SBMA. Treatment with pioglitazone (PG), an activator of PPARγ, improved the viability of the cellular model of SBMA. The oral administration of PG also improved the behavioral and histopathological phenotypes of the transgenic mice. Furthermore, immunohistochemical and biochemical analyses demonstrated that the administration of PG suppressed oxidative stress, nuclear factor-κB (NFκB) signal activation and inflammation both in the spinal cords and skeletal muscles of the SBMA mice. These findings suggest that PG is a promising candidate for the treatment of SBMA.

Paeoniflorin eliminates a mutant AR via NF-YA-dependent proteolysis in spinal and bulbar muscular atrophy.

The accumulation of abnormal proteins is a common characteristic of neurodegenerative diseases. This accumulation reflects a severe disturbance of cellular homeostasis in pathogenic protein clearance. Here, we demonstrated that the activation of the two major proteolytic machineries, the molecular chaperone-ubiquitin proteasome system (UPS) and the autophagy system, were simultaneously enhanced by paeoniflorin (PF), a major component of Paeonia plants, and exerted therapeutic effects in models of spinal and bulbar muscular atrophy (SBMA). PF significantly increased the expression of nuclear factor-YA (NF-YA), which strongly upregulated the molecules involved in the proteolytic machinery [molecular chaperones, carboxyl terminus of Hsc70-interacting protein and transcription factor EB], which thus mitigated the behavioral and pathological impairments in an SBMA mouse model through the upregulation of pathogenic androgen receptor protein clearance in motor neurons and muscles. These findings demonstrated that PF is able to enhance both the UPS and autophagy systems by upregulating the expression of NF-YA, which promotes therapeutic effects in an SBMA model.

[Successful Postoperative Management of a Pediatric Patient with Renal Failure by Ultrasound-guided Transversus Abdominis Plane and Rectus Sheath Block].

We report the successful postoperative pain man- agement of a pediatric patient with end-stage renal failure by ultrasound-guided peripheral nerve block following peritoneal dialysis catheter surgery. A 2-year-old boy with kidney hypoplasia was scheduled for peritoneal dialysis catheter implantation under gen- eral anesthesia. Anesthesia was induced with nitrous oxide and sevoflurane in a slow incremental manner. Airway management was performed with i-gelo to minimize stress and to protect the cervical spine. Maintenance of anesthesia was achieved with sevoflu- rane and remifentanil. For postoperative analgesia, opi- oids were not used in order to avoid respiratory sup- pression or CO2 accumulation. Recovery from anesthe- sia was uneventful and the boy did not experience pain until the next morning.

[Anesthetic Management of Simultaneous Right Lobectomy and Esophagectomy with a Double-lumen Tracheal Tube and Bronchial Blocker].

Anesthestic management with prolonged one-lung ventilation is difficult, especially when the patient continues smoking habit. Here, we report a successful one-lung ventilation and protection with combined use of double-lumen endotracheal tube and bronchial blocker. A 68-year-old man (height 153 cm; weight, 45 kg) was scheduled for simultaneous surgery of right lobectomy and esophagectomy. He kept smoking to the operation day. To protect the ventilated lung, we guided the bronchial lumen of the DLT to the left bronchus under fiberoptic bronchoscope (FOB) guide and inflated the bronchial cuff. Next, we inserted the bronchial blocker from the tracheal lumen of the DLT and inflated the cuff in the left bronchus under FOB guidance. We performed continuous suctioning of the right trachea via the inner lumen of BB. During the operation, non-negligible amount of blood and sputum was aspirated from the inner lumen of the BB. Furthermore, there was no visible blood inflow in the left bronchus. We could protect the ventilated lung with double cuff, i. e. bronchial cuff of DLT in the left bronchus and BB cuff in the right bronchus. Simultaneous operation was uneventfully performed and no oxygenation or ventilation trouble was observed during the operation.

Identification and characterization of GABA(A) receptor autoantibodies in autoimmune encephalitis.

Autoimmune forms of encephalitis have been associated with autoantibodies against synaptic cell surface antigens such as NMDA- and AMPA-type glutamate receptors, GABA(B) receptor, and LGI1. However, it remains unclear how many synaptic autoantigens are yet to be defined. Using immunoproteomics, we identified autoantibodies against the GABA(A) receptor in human sera from two patients diagnosed with encephalitis who presented with cognitive impairment and multifocal brain MRI abnormalities. Both patients had antibodies directed against the extracellular epitope of the ß3 subunit of the GABA(A) receptor. The ß3-subunit-containing GABA(A) receptor was a major target of the patients' serum antibodies in rat hippocampal neurons because the serum reactivity to the neuronal surface was greatly decreased by 80% when the ß3 subunit was knocked down. Our developed multiplex ELISA testing showed that both patients had similar levels of GABA(A) receptor antibodies, one patient also had a low level of LGI1 antibodies, and the other also had CASPR2 antibodies. Application of the patients' serum at the time of symptom presentation of encephalitis to rat hippocampal neuron cultures specifically decreased both synaptic and surface GABA(A) receptors. Furthermore, treatment of neurons with the patients' serum selectively reduced miniature IPSC amplitude and frequency without affecting miniature EPSCs. These results strongly suggest that the patients' GABA(A) receptor antibodies play a central role in the patients' symptoms. Therefore, this study establishes anti-GABA(A) receptor encephalitis and expands the pathogenic roles of GABA(A) receptor autoantibodies.

Decreased expression of lysophosphatidylcholine (16:0/OH) in high resolution imaging mass spectrometry independently predicts biochemical recurrence after surgical treatment for prostate cancer.

BACKGROUND: Human prostate cancers are highly heterogeneous, indicating a need for various novel biomarkers to predict their prognosis. Lipid metabolism affects numerous cellular processes, including cell growth, proliferation, differentiation, and motility. Direct profiling of lipids in tissue using high-resolution matrix-assisted laser desorption/ionization imaging mass spectrometry (HR-MALDI-IMS) may provide molecular details that supplement tissue morphology. METHODS: Prostate tissue samples were obtained from 31 patients, with localized prostate cancer who underwent radical prostatectomy. The samples were assessed by HR-MALDI-IMS in positive mode, with the molecules identified by tandem mass spectrometry (MS/MS). The effect of identified molecules on prostate specific antigen recurrence free survival after radical prostatectomy was determined by Cox regression analysis and by the Kaplan-Meier method. RESULTS: Thirteen molecules were found to be highly expressed in prostate tissue, with five being significantly lower in cancer tissue than in benign epithelium. MS/MS showed that these molecules were [lysophosphatidylcholine (LPC)(16:0/OH)+H](+), [LPC(16:0/OH)+Na](+), [LPC(16:0/OH)+K](+), [LPC(16:0/OH)+matrix+H](+), and [sphingomyelin (SM)(d18:1/16:0)+H](+). Reduced expression of LPC(16:0/OH) in cancer tissue was an independent predictor of biochemical recurrence after radical prostatectomy. CONCLUSIONS: HR-MALDI-IMS showed that the expression of LPC(16:0/OH) and SM(d18:1/16:0) was lower in prostate cancer than in benign prostate epithelium. These differences in expression of phospholipids may predict prostate cancer aggressiveness, and provide new insights into lipid metabolism in prostate cancer.

Laryngoscopy facilitates successful i-gel insertion by novice doctors: a prospective randomized controlled trial.

BACKGROUND: This study investigated the hypothesis that the efficacy of insertion of the supraglottic device i-gel(®) (i-gel) can be improved by laryngoscopy and can provide better sealing pressure in anesthetized patients by novice doctors. METHODS: Eighty-four adult patients were assigned to the laryngoscopy group (L group, 42 patients) or control group (i.e., conventional blind insertion; C group, 42 patients). Anesthesia was induced with propofol and remifentanil, and rocuronium 0.6-0.9 mg/kg was administered. The number of attempts until successful insertion, sealing pressure, vital sign changes upon insertion, and subjective difficulty of insertion by novice doctors were compared between the groups. RESULTS: The total number of insertion attempts was one (L group 36 cases, C group 23 cases), two (L group 6 cases, C group 18 cases), and three (L group 0 case, C group 1 case), with significant differences between groups (P = 0.007). The sealing pressure was significantly higher in the L group than in the C group (L group 22.3 ± 2.6 cmH2O, C group 19.5 ± 2.7 cmH2O, P < 0.001). Vital sign changes (heart rate and blood pressure) did not differ between the two groups. The subjective difficulty of insertion was significantly lower in the L group than in the C group (L group 26.8 ± 11.8 mm, C group 47.0 ± 15.1 mm, P < 0.001). The incidence of postoperative pharyngeal pain was significantly lower in the L group than in the C group (P < 0.001), while the incidence of hoarseness did not differ between the two groups (P = 1.00). CONCLUSION: Our results suggest that laryngoscopy facilitates i-gel insertion by novice doctors, as reflected in the rate of successful insertions, higher sealing pressure, and lower subjective difficulty of insertion in anesthetized patients.

[Comparison of the Intracuff Pressure Increase by Upper Gastrointestinal Endoscope Insertion in TaperGuard Cuffed Tube and High-volume Low Pressure Cuffed Tracheal Tube: A Porcine Larynx Model Study].

BACKGROUND: The purpose of this study was to compare the upper gastrointestinal endoscope (UGE) insertion-mediated cuff pressure increase between a tracheal tube with a tapered cuff (Taper) and or conventional high volume low pressure cuff (HVLP) utilizing a porcine larynx model. METHODS: The automated cuff pressure was adjusted to 10, 20, and 30 cmH2O. The Taper and HVLP cuff pressure increases by UGE insertion were measured. RESULTS: Significant cuff pressure increase was observed by UGE insertion regardless of initial cuff pressure. The cuff pressure of the Taper was significantly lower than that of the HVLP by UGE insertion. CONCLUSIONS: These findings suggest that the Taper may be more effective than the HVLP in preventing tracheal tube cuff increase by UGE insertion.

[Successful Tracheal Intubation Using Videolaryngoscope in an Infant with Massive Tongue Swelling].

We report use of videolaryngoscope for difficult airway management in an infant with severe tongue swelling after laceration repair. A 3-month-old male infant was transferred to our hospital for respiratory difficulty. He could not open his mouth sufficiently, and the examination revealed massive swelling of the left side of the tongue. Emergent surgical repair of the tongue was scheduled, anticipating a difficult airway. The venous line was kept patent preoperatively, and 8% sevoflurane was administered maintaining spontaneous ventilation. We then inserted the Pentax Airway Scope with an infant-sized Intlock (AWS-I) from the right side of the mouth and obtained a good view at laryngoscopy. A 3.5-mm tracheal tube was passed uneventfully under the view of AWS-I. The AWS-I is useful for difficult airway management in infants, preserving spontaneous ventilation.

[Nitrous Oxide Exposure-mediated Increases in Cuff Pressure: A Comparison of Disposable Type and Re-use Type air-Q Devices].

UNLABELLED: BaCKGROUND: The present study aimed to compare nitrous oxide-mediated increases in cuff pressure between the disposable type air-Q (air-Q-DT) and re-use type air-Q (air-Q-RU) in a simulated adult airway model. METHODS: Automated cuff pressure was adjusted to 10, 20, and 30 cmH2O. The air-Q-DT and air-Q-RU were exposed to 80% nitrous oxide and cuff pressure was measured 15 and 30 minutes later. RESULTS: Cuff pressure of the air-Q-DT was significantly lower than that of the air-Q-RU after 15 and 30 minutes, regardless of the initial pressure. CONCLUSIONS: The polyvinyl chloride-based air-Q-DT may be more effective than the silicon-based air-Q-RU in preventing hyperinflation of the tracheal tube cuff in response to nitrous oxide exposure.

p62/SQSTM1 differentially removes the toxic mutant androgen receptor via autophagy and inclusion formation in a spinal and bulbar muscular atrophy mouse model.

Polyglutamine (polyQ) diseases are inherited neurodegenerative disorders that are caused by the expansion of trinucleotide CAG repeats in the causative genes. Spinal and bulbar muscular atrophy (SBMA) is an inherited motor neuron disease that is caused by the expansion of a polyQ tract within the androgen receptor (AR). p62 is a ubiquitin- and light-chain 3-binding protein that is known to regulate the degradation of targeted proteins via autophagy and inclusion formation. In this study, we examined the effects of p62 depletion and overexpression on cultured cells and in a transgenic mouse model that overexpressed the mutant AR. Here, we demonstrate that depletion of p62 significantly exacerbated motor phenotypes and the neuropathological outcome, whereas overexpression of p62 protected against mutant AR toxicity in SBMA mice. Depletion of p62 significantly increased the levels of monomeric mutant AR and mutant AR protein complexes in an SBMA mouse model via the impairment of autophagic degradation. In addition, p62 overexpression improved SBMA mouse phenotypes by inducing cytoprotective inclusion formation. Our results demonstrate that p62 provides two different therapeutic targets in SBMA pathogenesis: (1) autophagy-dependent degradation and (2) benevolent inclusion formation of the mutant AR.

Morphological and genetic diversity of Briareum (Anthozoa: Octocorallia) from the Ryukyu Archipelago, Japan.

The primary problem hindering the study of octocorals is the disordered situation regarding their taxonomy, chiefly caused by insufficient knowledge of valid morphological taxonomic characters. Briareum is an octocoral genus found in the Atlantic and Pacific in shallow tropical and subtropical waters, and occurs in both encrusting and branching colony forms. Their simple morphology and morphological plasticity have hindered taxonomic understanding of this genus. In this study three morphologically distinct types (= type-1, -2, and -3) of Briareum from the Ryukyu Archipelago and their genetic diversity were examined. Colony, anthostele morphology, and sclerite length were examined for each type. Four molecular markers (mitochondrial cytochrome c oxidase subunit 1, mitochondrial mismatch repair gene, nuclear 18S ribosomal DNA, internal transcribed spacer 2 (ITS2)) were used to evaluate molecular phylogenetic status of these variations. Although one morphological type ("deep" small colonies, = type-3) showed small differences in nuclear ITS2 sequences compared to the other two types, the remaining types had identical sequences for all molecular markers examined. The results suggest extremely low genetic diversity despite highly variable morphology of Briareum species in Okinawa. Nevertheless, considering the distribution patterns and discontinuous morphology of type-3 compared to the other two morphotypes, genetic isolation of type-3 is plausible. In Briareum, small variances in nuclear ITS2 sequences of type-3 may have much more importance than in molecular phylogenies of other octocorals. Further phylogenetic investigations and comparison with Briareum specimens from other regions are necessary to conclusively taxonomically identify the three types.

[Development of a preoperative criterion to select candidates for nerve-sparing radical prostatectomy at Kyoto University Hospital].

Neurovascular bundle (NVB) preservation is a mandatory procedure to maintain erectile function of localized prostate cancer patients after radical prostatectomy (RP). However, in terms of cancer control, indications to select appropriate patients for nerve-sparing RP are still controversial. In this study, we examined the pathological findings of RP specimens to develop a preoperative criterion for NVB preservation during RP. The study included 76 patients who underwent RP at our institution from 2006 to 2008, and we retrospectively analyzed RP specimens pathologically. The distance between NVB and foci of prostate cancer was measured in 135 prostate sides, and preoperative factors which predict the distance of ≤2 mm was evaluated. Univariate analysis showed that side-specific positive biopsy core rate ≥33.3%, side-specific maximum tumor length in biopsy core ≥5 mm and side-specific tumor involvement rate in biopsy core ≥50% was associated with the risk of the distance of ≤2 mm. Multivariate analysis revealed that side-specific positive biopsy core rate ≥33.3% was the only significant predictor of the ipsilateral NVB-tumor distance ≤2 mm (p = 0.0055, odds ratio 3.49). Based on this study, a nerve-sparing criterion of ＜33.3% side-specific percent positive biopsy core was developed at our institution. Prospective data on patients who were applied this criterion are needed to evaluate its clinical safety and feasibility.

[Successful awake tracheal intubation in the sitting position using the Pentax-AWS Airwayscope in a patient with hypopharyngeal cancer and gastroesophageal regurgitation].

We report the successful awake tracheal intubation in a patient with hypopharyngeal cancer and gastroesophageal regurgitation with the TaperGuard Evac tracheal tube (TaperGuard) and Pentax-AWS Airwayscope (AWS). A 63-year-old man with hypopharyngeal cancer with invasion to the glottis was scheduled for total laryngectomy under general anesthesia. He had undergone thoracic esophagectomy and could not maintain supine position due to severe gastroesophageal regurgitation. To avoid vomiting after induction of anesthesia, we planned awake intubation in the sitting position with the AWS. After topical anesthesia with 8% lidocaine and infusion of fentanyl and continuous dexmedetomidine, the AWS was inserted into his mouth in the sitting position from the cranial side. The AWS allowed visualizing the glottis avoiding the cancer, leading to safe placement of the tracheal tube.