Oral Colchicine and Low-Dose Aspirin Combination Therapy for Non-elderly, Non-severe, Early Time From Onset, Adult Outpatients with Coronavirus Disease 2019 (COVID-19) during "The Fifth Pandemic Wave" in Japan.

BACKGROUND: Treatment with antiviral drugs for non-severe, early time from onset, adult outpatients with Coronavirus Disease 2019 (COVID-19) had not been established in 2021. However, some new variants of SARS-CoV-2 had caused rapid exacerbation and hospitalization among non-elderly outpatients with COVID-19, contributing to widespread crises within healthcare systems. METHODS: From July to October 2021, we urgently assessed a therapeutic program using oral colchicine (1.0 mg loading dose, followed approximately half a day later by 0.5 mg twice daily for 5 days, and then 0.5 mg once daily for 4 days) and low-dose aspirin (100 mg once daily for 10 days), for non-elderly, non-severe, early time from onset, adult outpatients with COVID-19. To verify its effectiveness, we set loxoprofen as a control arm, and com parison of these two arms was performed. The primary outcomes were hospitalization, criticality, and death rates. RESULTS: Thirty-eight patients (23 receiving colchicine and low-dose aspirin [CA]; 15 receiving loxoprofen [LO]) were evaluated. Hospitalization rate was lower in the CA group (1/23; 4.3%) than in the LO group (2/15; 13.3%); however, no significant difference was found between the two groups (p=0.34). No critical cases, deaths, or severe adverse events were found in either group. CONCLUSIONS: Our CA regimen did not show superiority over LO treatment. However, our clinical experience should be recorded as part of community health care activities carried out in Kurume City against the unprece dented COVID-19 pandemic.

Association Between Acute Kidney Injury and the Trendelenburg Position Angle During Robot-assisted Radical Prostatectomy.

BACKGROUND/AIM: Robot-assisted radical prostatectomy (RARP) has been widely adopted as the standard treatment for localized prostate cancer. RARP is safer and results in better oncological control than conventional open total prostatectomy. However, it has also been reported that acute kidney injury (AKI) can be caused by the use of carbon dioxide pneumoperitoneum and a steep Trendelenburg position. We investigated the incidence of AKI after RARP and its relationship with the Trendelenburg position angle. PATIENTS AND METHODS: Seventy-seven patients underwent RARP at our institution. They were divided into two groups: Those in which a Trendelenburg position with the head down at 20 degrees was employed (group A) and those in which a Trendelenburg position with the head down at 25 degrees was used (group B). To detect AKI, the serum creatinine concentration was measured at the following four points: Prior to surgery, on postoperative day 0 (immediately after RARP), and on postoperative days 1 and 6 after RARP. RESULTS: The incidence of AKI on POD 0 was lower in group B than in group A (p=0.0408). On POD 6, the renal function of all patients had improved to preoperative levels. Hypertension was a predictor of the incidence of AKI immediately after RARP. CONCLUSION: Although there was a significant Trendelenburg position angle-dependent difference in the incidence of AKI immediately after RARP, it was temporary. Hypertension is a predictor of AKI immediately after RARP. It is recommended that a 25-degree Trendelenburg position angle should be employed during RARP.

Parameter variation effects on millimeter wave dosimetry based on precise skin thickness in real rats.

This study presents a parametric analysis of the steady-state temperature elevation in rat skin models due to millimeter wave exposure at frequencies from 6-100 GHz. The statistical data of the thickness of skin layers, namely epidermis, dermis, dermal white adipose tissue, and panniculus carnosus, were measured for the first time using the excised tissues of real male Sprague-Dawley rats. Based on the precise structure obtained from the histological analysis of rat skin, we solve the bioheat transfer equation to investigate the effects of changes in parameters, such as body parts and thermal constants, on the absorbed power density and temperature elevation of biological tissues. Owing to the notably thin dermal white adipose tissue layer, the surface temperature elevation in the rat head and dorsal skin at 6-100 GHz is 52.6-32.3% and 83.3-58.8% of the average values of different human skin models, respectively. Our results also reveal that the surface temperature elevation of rat skin may correlate with the tissue thickness and deep blood perfusion rates.

Excessive whole-body exposure to 28 GHz quasi-millimeter wave induces thermoregulation accompanied by a change in skin blood flow proportion in rats.

Introduction: Limited information is available on the biological effects of whole-body exposure to quasi-millimeter waves (qMMW). The aim of the present study was to determine the intensity of exposure to increase body temperature and investigate whether thermoregulation, including changes in skin blood flow, is induced in rats under whole-body exposure to qMMW. Methods: The backs of conscious rats were extensively exposed to 28 GHz qMMW at absorbed power densities of 0, 122, and 237 W/m2 for 40 minutes. Temperature changes in three regions (dorsal and tail skin, and rectum) and blood flow in the dorsal and tail skin were measured simultaneously using fiber-optic probes. Results: Intensity-dependent temperature increases were observed in the dorsal skin and the rectum. In addition, skin blood flow was altered in the tail but not in the dorsum, accompanied by an increase in rectal temperature and resulting in an increase in tail skin temperature. Discussion: These findings suggest that whole-body exposure to qMMW drives thermoregulation to transport and dissipate heat generated on the exposed body surface. Despite the large differences in size and physiology between humans and rats, our findings may be helpful for discussing the operational health-effect thresholds in the standardization of international exposure guidelines.

Intensity-dependent Temperature Rise Induced by Local Exposure to 26.5 GHz Quasi-Millimeter-Wave in Rat.

BACKGROUND/AIM: The widespread use of fifth-generation 5G millimeter-waves (MMW) generates concern about potential adverse health effects. The latest international guidelines for MMW exposure adopt an absorbed power density (APD) of 200 W/m2 to avoid a local temperature rise of 5°C in human tissues as an operational adverse health effect threshold. However, because APD is estimated by simulations using human tissue models, it is unknown whether a similar value can be confirmed for living tissues. The aim of this study was to investigate the relationship between APD and skin temperature rise in vivo, and to validate the estimated values. MATERIALS AND METHODS: The rat dorsal skin was locally exposed to a 26.5 GHz quasi-MMW (qMMW) for 18 min using a patch antenna. The qMMW exposure intensities estimated by dosimetry were set to 0-500 W/m2 of APD. The temperatures in the dorsal skin and rectum were simultaneously measured during exposure. RESULTS: The qMMW-induced local temperature increase at different sites. The dorsal skin temperature increased by approximately 11.3°C at a maximum intensity of 500 W/m2, but the rectal temperature increased by only 0.6°C, indicating highly localized effects of exposure to rats. A significant correlation was observed between APD and skin temperature rise. The relationship provided a linear regression model, and a temperature rise of less than 5°C was estimated in the skin exposed to 200 W/m2 of APD. CONCLUSION: These results suggest that the operational threshold for the MMW exposure guidelines is valid under the present experimental conditions using rats.

Incomplete hippocampal inversion in patients with mutations in genes involved in sonic hedgehog signaling.

Sonic hedgehog (Shh) signaling pathways are known to play an important role in the morphological development of the hippocampus in vivo, but their actual roles in humans have not been clarified. Hypothalamic hamartoma (HH) is known to be associated with germline or somatic gene mutations of Shh signaling. We hypothesized that patients with HH and mutations of Shh-related genes also show hippocampal maldevelopment and an abnormal hippocampal infolding angle (HIA). We analyzed 45 patients (age: 1-37 years) with HH who underwent stereotactic radiofrequency thermocoagulation and found Shh-related gene mutations in 20 patients. In addition, 44 pediatric patients without HH (age: 2-25 years) who underwent magnetic resonance imaging (MRI) examinations under the same conditions during the same period were included in this study as a control group. HIA evaluated on MRI was compared between patients with gene mutations and the control group. The median HIA at the cerebral peduncle slice in patients with the gene mutation was 74.36° on the left and 76.11° on the right, and these values were significantly smaller than the corresponding values in the control group (80.46° and 80.56°, respectively, p < 0.01). Thus, mutations of Shh-related genes were correlated to incomplete hippocampal inversion. The HIA, particularly at the cerebral peduncle slice, is a potential indicator of abnormalities of the Shh-signaling pathway.

Efficacy and Safety of Tolvaptan for Patients With Autosomal Dominant Polycystic Kidney Disease in Real-world Practice: A Single Institution Retrospective Study.

BACKGROUND/AIM: We evaluated the efficacy and safety of tolvaptan for autosomal dominant polycystic kidney disease (ADPKD) in real-world practice. PATIENTS AND METHODS: We retrospectively reviewed the cases of 27 patients who had been diagnosed with ADPKD between January 2014 and December 2022. Among them, 14 patients received tolvaptan (60 mg/day; morning: 45 mg, night: 15 mg) after being admitted for 2 days. In the outpatient clinic, blood and urine samples were taken monthly. RESULTS: The mean age, pretreatment estimated glomerular filtration rate (eGFR), treatment duration, and total kidney volume were 60 years, 45.6 ml/min/1.73 m2, 2.8 years, and 2,390 ml, respectively. One month later, the patients' renal dysfunction had worsened slightly, and their serum sodium concentrations had significantly increased. After one year, the mean reduction in the eGFR was -5.5 ml/min/1.73 m2 Moreover, at 3 years the patients' renal function was stable. No hepatic dysfunction or electrolyte abnormalities were noted, although discontinuation occurred in two cases. Tolvaptan treatment is considered to be safe. CONCLUSION: Tolvaptan was effective against ADPKD in a real-world setting. Moreover, the safety of tolvaptan was confirmed.

Laparoscopic redo pyeloplasty with a buccal mucosal graft.

Introduction: Redo pyeloplasty can be difficult due to scar tissue or fibrosis. Ureteral reconstruction with a buccal mucosal graft is performed safely and successfully, but most reports of ureteral reconstruction using a buccal mucosal graft are of robot-assisted surgery, with few reports of laparoscopic-assisted surgery. A case of laparoscopic-assisted redo pyeloplasty using a buccal mucosal graft is presented. Case presentation: A 53-year-old woman was diagnosed with ureteropelvic junction obstruction, and a double-J stent was placed to relieve backache. She visited our hospital 6 months after double-J stent placement. Three months later, laparoscopic pyeloplasty was performed. At 2 months postoperatively, anatomic stenosis occurred. Holmium laser endoureterotomy and balloon dilation were performed; however, the anatomic stenosis recurred, and laparoscopic redo pyeloplasty with a buccal mucosal graft was performed. After redo pyeloplasty, obstruction was improved, and her symptoms disappeared. Conclusion: This is the first case of using a buccal mucosal graft for laparoscopic pyeloplasty in Japan.

Renal Impairment: A Major Adverse Event in Prostate Cancer Patients Treated With Androgen Deprivation Therapy.

Androgen deprivation therapy (ADT) is the major treatment for advanced prostate cancer (PCa). Although ADT has been shown to improve oncological outcomes against PCa, it can also induce various adverse events, such as loss of libido, gynecomastia, fatigue, hot flashes, anemia, obesity, insulin resistance, dyslipidemia, cardiovascular events, and acute kidney injury (AKI). ADT reduces testosterone levels; consequently, ADT may antagonize the vasodilatory effects of testosterone on renal blood vessels, which could negatively affect renal tubular function. However, the renal impairment due to ADT is transient; i.e., it improves after the discontinuation of ADT. The recovery of serum testosterone levels may contribute to the amelioration of renal impairment induced by ADT. Serum testosterone levels are probably implicated in these changes, but the mechanism has not been studied in detail. With regard to the preservation of renal function and the anti-cancer effect of PCa, intermittent ADT may be a useful treatment for PCa. This is a review of the recent reports on the mechanism, current status, and prevention of renal impairment induced by ADT; future prospects in this field are also discussed.

A hydrolysate of poly-trans-[(2-carboxyethyl)germasesquioxane] (Ge-132) suppresses Cav3.2-dependent pain by sequestering exogenous and endogenous sulfide.

Poly-trans-[(2-carboxyethyl)germasesquioxane] (Ge-132), an organogermanium, is hydrolyzed to 3-(trihydroxygermyl)propanoic acid (THGP) in aqueous solutions, and reduces inflammation, pain and cancer, whereas the underlying mechanisms remain unknown. Sulfides including H2S, a gasotransmitter, generated from l-cysteine by some enzymes including cystathionine-γ-lyase (CSE), are pro-nociceptive, since they enhance Cav3.2 T-type Ca2+ channel activity expressed in the primary afferents, most probably by canceling the channel inhibition by Zn2+ linked via coordinate bonding to His191 of Cav3.2. Given that germanium is reactive to sulfur, we tested whether THGP would directly trap sulfide, and inhibit sulfide-induced enhancement of Cav3.2 activity and sulfide-dependent pain in mice. Using mass spectrometry and 1H NMR techniques, we demonstrated that THGP directly reacted with sulfides including Na2S and NaSH, and formed a sulfur-containing reaction product, which decreased in the presence of ZnCl2. In Cav3.2-transfected HEK293 cells, THGP inhibited the sulfide-induced enhancement of T-type Ca2+ channel-dependent membrane currents. In mice, THGP, administered systemically or locally, inhibited the mechanical allodynia caused by intraplantar Na2S. In the mice with cyclophosphamide-induced cystitis and cerulein-induced pancreatitis, which exhibited upregulation of CSE in the bladder and pancreas, respectively, systemic administration of THGP as well as a selective T-type Ca2+ channel inhibitor suppressed the cystitis-related and pancreatitis-related visceral pain. These data suggest that THGP traps sulfide and inhibits sulfide-induced enhancement of Cav3.2 activity, leading to suppression of Cav3.2-dependent pain caused by sulfide applied exogenously and generated endogenously.

Outcomes of dutasteride discontinuation in patients with benign prostatic hypertrophy.

To the Editor, Benign prostatic hyperplasia (BPH) is a common cause of lower urinary tract symptoms (LUTS) in elderly males. The current guidelines recommend the use of a 5-alpha reductase inhibitor (5ARI) to treat males with moderate-to-severe LUTS and an enlarged prostate. Combination therapy with an alpha blocker and a 5ARI has proven effective at ameliorating LUTS and reducing the total prostate volume (TPV) and the risk of the disease progression.

The choice of therapeutic agent in female overactive bladder patients in real-world practice.

OBJECTIVE: The reasons why anticholinergic drugs or ß3 adrenergic agonists are selected as treatments for overactive bladder (OAB) are unclear. The aim of this study was to investigate the background data of female OAB patients that were prescribed anticholinergic drugs or ß3 adrenergic agonists in a real-world setting. MATERIALS AND METHODS: Between January 2013 and December 2014, 75 patients who had been diagnosed with OAB were included in this study. Administered medications, age, the persistence on treatment rate at one-year, medical history, pretreatment total Overactive Bladder Symptom Score (OABSS), pretreatment score for each OABSS factor, body mass index (BMI), and various comorbidities were evaluated retrospectively. Since there were many types of anticholinergic drugs and few patients, we grouped the patients into those that were prescribed anticholinergic drugs (group A) and those that were prescribed ß3 adrenergic agonists (group B). RESULTS: 75 patients (29 in group A and 46 in group B) were included in this study. There were no significant differences in age, BMI, obesity, medical history, pretreatment total OABSS, or pretreatment score for each OABSS factor. There was a significant difference in the post-voiding residual urine volume (PVR) between the groups (group A: 22 ml, group B: 9 ml; p = 0.0252). The 1-year persistence on treatment rate was 28% in both groups. CONCLUSIONS: There were no significant differences in clinical characteristics of patients who were prescribed anticholinergics and ß3 adrenergic agonists for OAB treatment, but a marginal difference of PVR value before treatment. The 1-year persistence rates of anticholinergic drugs and ß3 adrenergic agonists were considered to be almost equivalent.

Plasma exchange and infliximab as a third-line therapy for refractory infantile Kawasaki disease.

BACKGROUND: The treatment for Kawasaki disease (KD) patients refractory to intravenous immunoglobulin (IVIG) therapy is still controversial, and the efficacy of plasma exchange (PE) and infliximab (IFX) therapy for infantile KD is unknown. METHODS: A total of 22 infantile KD patients refractory to initial and additional IVIG, who received either PE or IFX as third-line therapy from October 2008 to February 2020 were examined retrospectively. The patients' sex, age, days of first IVIG, days of PE or IFX therapy, laboratory data preceding PE or IFX therapy, coronary artery lesions (CALs), and adverse effects were investigated. RESULTS: Thirteen patients received PE and nine patients received IFX as the third-line therapy. For the median age at onset, the median days of first IVIG and PE or IFX, and pre-PE or IFX therapy blood test results, there were no significant between-group differences. At admission, and before and after the third-line therapy, there were also no significant differences in occurrence of CALs. The frequency of serious adverse events was significantly higher in the PE group than in the IFX group. CONCLUSIONS: Although there were no significant differences in patient background, blood test results, or frequency of CALs, the frequency of adverse events was significantly higher in the PE group. With the trend of expansion of IFX therapy for KD patients refractory to IVIG, the role of PE as the additional therapy may become more limited.

A Special Approach for Stereotactic Radiofrequency Thermocoagulation of Hypothalamic Hamartomas With Bilateral Attachments to the Hypothalamus: The Transthird Ventricular Approach to the Contralateral Attachment.

BACKGROUND: Disconnection surgery for the treatment of epileptic hypothalamic hamartomas (HHs) is strategically difficult in cases with complex-shaped HHs, especially with bilateral hypothalamic attachments, despite its effectiveness. OBJECTIVE: To evaluate the feasibility of a new approach for stereotactic radiofrequency thermocoagulation (SRT) using penetration of the third ventricle (SRT-TT) aiming to disconnect bilateral hypothalamic attachments in a single-staged, unilateral procedure. METHODS: Ninety patients (median age at surgery, 5.0 years) who had HHs with bilateral hypothalamic attachments and were followed for at least 1 year after their last SRT were retrospectively reviewed. RESULTS: Thirty-three patients underwent SRT-TT as initial surgery. Of the 58 patients after mid-2013 when SRT-TT was introduced, 33 underwent SRT-TT and 12 (20.7%) required reoperation (ReSRT), whereas 20 of 57 patients (35.1%) without SRT-TT underwent reoperation. Reoperation was required in significantly fewer patients after mid-2013 (n = 12 of 58, 20.7%) than before mid-2013 (n = 15 of 32, 46.9%) ( P = .01). Final seizure freedoms were not different between before and after mid-2013 (gelastic seizure freedom, n = 30 [93.8%] vs n = 49 [84.5%] and other types of seizure freedom, n = 21 of 31 [67.7%] vs n = 32 of 38 [84.2%]). Persistent complications were less in SRT-TT than in ReSRT using the bilateral approach, but not significantly. However, hormonal replacement was required significantly more often in ReSRT using the bilateral approach (4 of 9, 44.4%) than in SRT-TT (3 of 32, 9.4%) ( P = .01). CONCLUSION: SRT-TT enabled disconnection of bilateral attachments of HHs in a single-staged procedure, which reduced the additional invasiveness of reoperation. Moreover, SRT-TT reduced damage to the contralateral hypothalamus, with fewer endocrinological complications than the bilateral approach.

Surgical Strategy for Directional Deep Brain Stimulation.

Deep brain stimulation (DBS) is a well-established treatment for drug-resistant involuntary movements. However, the conventional quadripole cylindrical lead creates electrical fields in all directions, and the resulting spread to adjacent eloquent structures may induce unintended effects. Novel directional leads have therefore been designed to allow directional stimulation (DS). Directional leads have the advantage of widening the therapeutic window (TW), compensating for slight misplacement of the lead and requiring less electrical power to provide the same effect as a cylindrical lead. Conversely, the increase in the number of contacts from four to eight and the addition of directional elements has made stimulation programming more complex. For these reasons, new treatment strategies are required to allow effective directional DBS. During lead implantation, the directional segment should be placed in a "sweet spot," and the orientation of the directional segment is important for programming. Trial-and-error testing of a large number of contacts is unnecessary, and efficient and systematic execution of the programmed procedure is desirable. Recent improvements in imaging technologies have enabled image-guided programming. In the future, optimal stimulations are expected to be programmed by directional recording of local field potentials.

Changes in prognostic nutritional index during hospitalization and outcomes in patients with acute heart failure.

Although the prognostic nutritional index (PNI) is reported as a prognosticator in patients with heart failure (HF), that is evaluated usually on one occasion, and any changes in PNI during hospitalization are not considered. This study aimed to assess between changes in the PNI during hospitalization and outcomes in patients with acute HF. We enrolled 141 patients (median age, 84 years, 75 male) admitted to our hospital for the treatment of acute HF. The PNI was calculated on admission and at discharge based on the original report. According to the PNI change during hospitalization, patients were classified as either improved (PNI at discharge ≥ PNI on admission) or deteriorated (PNI at discharge < PNI on admission). Primary outcomes were all-cause death or unplanned hospitalization due to HF within the first year. Forty-nine events occurred (19 deaths, 30 HF hospitalizations). The event-free survival rate determined by Kaplan-Meier analysis was significantly higher in patients in the improved group (log-rank test, P < 0.0001), regardless of the PNI value on admission. Multivariate analysis showed that younger age (HR 1.06, 95% CI 1.01-1.11, P = 0.016), higher body mass index (HR 0.90, 95% CI 0.82-0.98, P = 0.021) and the PNI in the improved group (HR 0.30, 95% CI 0.14-0.57, P = 0.0006) were independently associated with favorable outcomes. In conclusion, changes in nutritional status during hospitalization, evaluated using the PNI on admission and at discharge, were independently associated with 1-year outcomes in patients with acute HF.

Novel 60 GHz Band Spatial Synthetic Exposure Setup to Investigate Biological Effects of 5G and Beyond Wireless Systems on Human Body.

The global spread of 5th generation (5G) wireless systems causes some concern about health effects of millimeter waves (MMW). To investigate biological effects of local exposure to 5G-MMW on human body, a novel 60 GHz band exposure setup was developed, and its performance was validated. A spatial synthetic beam-type exposure setup using two dielectric lens antennas was proposed to achieve high intensity 60 GHz irradiation to the target area of human skin. Variety distributions and intensities of electromagnetic fields at the exposed area, which is modified by incident angles of the combined beams, were simulated using finite-difference time-domain methods. The exposure performance we estimated was verified by temperature elevations of surface in a physical arm-shaped silicone phantom during the MMW exposure. The interference fringes generated in the exposed area due to the combined two-directional beam radiations were observed both in the simulation and in the phantom experiment but eliminated by applying an orthogonalizing polarized feeding structure. Under these exposure conditions, the local temperature changes, which could evoke warmth sensations, were obtained at the target area of the human forearm skin, which means the achievement of exposure performance we intended.

Deep learning-based diagnosis of temporal lobe epilepsy associated with hippocampal sclerosis: An MRI study.

PURPOSE: The currently available indicators-sensitivity and specificity of expert radiological evaluation of MRIs-to identify mesial temporal lobe epilepsy (MTLE) associated with hippocampal sclerosis (HS) are deficient, as they cannot be easily assessed. We developed and investigated the use of a novel convolutional neural network trained on preoperative MRIs to aid diagnosis of these conditions. SUBJECTS AND METHODS: We enrolled 141 individuals: 85 with clinically diagnosed mesial temporal lobe epilepsy (MTLE) and hippocampal sclerosis International League Against Epilepsy (HS ILAE) type 1 who had undergone anterior temporal lobe hippocampectomy were assigned to the MTLE-HS group, and 56 epilepsy clinic outpatients diagnosed as nonepileptic were assigned to the normal group. We fine-tuned a modified CNN (mCNN) to classify the fully connected layers of ImageNet-pretrained VGG16 network models into the MTLE-HS and control groups. MTLE-HS was diagnosed using MRI both by the fine-tuned mCNN and epilepsy specialists. Their performances were compared. RESULTS: The fine-tuned mCNN achieved excellent diagnostic performance, including 91.1% [85%, 96%] mean sensitivity and 83.5% [75%, 91%] mean specificity. The area under the resulting receiver operating characteristic curve was 0.94 [0.90, 0.98] (DeLong's method). Expert interpretation of the same image data achieved a mean sensitivity of 73.1% [65%, 82%] and specificity of 66.3% [50%, 82%]. These confidence intervals were located entirely under the receiver operating characteristic curve of the fine-tuned mCNN. CONCLUSIONS: Deep learning-based diagnosis of MTLE-HS from preoperative MR images using our fine-tuned mCNN achieved a performance superior to the visual interpretation by epilepsy specialists. Our model could serve as a useful preoperative diagnostic tool for ascertaining hippocampal atrophy in patients with MTLE.