Coronavirus Disease 19 (COVID-19) Vaccine Effectiveness Against Symptomatic Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Infection During Delta-Dominant and Omicron-Dominant Periods in Japan: A Multicenter Prospective Case-control Study (Factors Associated with SARS-CoV-2 Infection and the Effectiveness of COVID-19 Vaccines Study).

BACKGROUND: Although several coronavirus disease 2019 (COVID-19) vaccines initially showed high efficacy, there have been concerns because of waning immunity and the emergence of variants with immune escape capacity. METHODS: A test-negative design case-control study was conducted in 16 healthcare facilities in Japan during the Delta-dominant period (August-September 2021) and the Omicron-dominant period (January-March 2022). Vaccine effectiveness (VE) against symptomatic severe acute respiratory syndrome coronavirus 2 infection was calculated for 2 doses for the Delta-dominant period and 2 or 3 doses for the Omicron-dominant period compared with unvaccinated individuals. RESULTS: The analysis included 5795 individuals with 2595 (44.8%) cases. Among vaccinees, 2242 (55.8%) received BNT162b2 and 1624 (40.4%) received messenger RNA (mRNA)-1273 at manufacturer-recommended intervals. During the Delta-dominant period, VE was 88% (95% confidence interval [CI], 82-93) 14 days to 3 months after dose 2 and 87% (95% CI, 38-97) 3 to 6 months after dose 2. During the Omicron-dominant period, VE was 56% (95% CI, 37-70) 14 days to 3 months since dose 2, 52% (95% CI, 40-62) 3 to 6 months after dose 2, 49% (95% CI, 34-61) 6+ months after dose 2, and 74% (95% CI, 62-83) 14+ days after dose 3. Restricting to individuals at high risk of severe COVID-19 and additional adjustment for preventive measures (ie, mask wearing/high-risk behaviors) yielded similar estimates, respectively. CONCLUSIONS: In Japan, where most are infection-naïve, and strict prevention measures are maintained regardless of vaccination status, 2-dose mRNA vaccines provided high protection against symptomatic infection during the Delta-dominant period and moderate protection during the Omicron-dominant period. Among individuals who received an mRNA booster dose, VE recovered to a high level.

Immune escape and waning immunity of COVID-19 monovalent mRNA vaccines against symptomatic infection with BA.1/BA.2 and BA.5 in Japan.

BACKGROUND: Repeated emergence of variants with immune escape capacity and waning immunity from vaccination are major concerns for COVID-19. We examined whether the surge in Omicron subvariant BA.5 cases was due to immune escape or waning immunity through vaccine effectiveness (VE) evaluation. METHODS: A test-negative case-control study was conducted in 16 clinics/hospitals during the BA.1/BA.2-dominant and BA.5-dominant periods. VE against symptomatic infection was estimated after adjusting for age, sex, comorbidity, occupation, testing frequency, prior infection, close contact history, clinic/hospital, week, and preventive measures. Absolute VE (aVE) was calculated for 2/3/4 doses, compared to the unvaccinated. Relative VE (rVE) was calculated, comparing 3 vs 2 and 4 vs 3 doses. RESULTS: 13,025 individuals were tested during the BA.1/BA.2-dominant and BA.5-dominant periods with similar baseline characteristics. For BA.1/BA.2, aVE was 52 % (95 %CI:34-66) 14 days-3 months post-dose 2, 42 % (29-52) > 6 months post-dose 2, 71 % (64-77) 14 days-3 months post-dose 3, and 68 % (52-79) 3-6 months post-dose 3. rVE was 49 % (38-57) 14 days-3 months post-dose 3 and 45 % (18-63) 3-6 months post-dose 3. For BA.5, aVE was 56 % (27-73) 3-6 months post-dose 2, 32 % (12-47) > 6 months post-dose 2, 70 % (61-78) 14 days-3 months post-dose 3, 59 % (48-68) 3-6 months post-dose 3, 50 % (29-64) > 6 months post-dose 3, and 74 % (61-83) ≥ 14 days post-dose 4. rVE was 56 % (45-65) 14 days-3 months post-dose 3, 39 % (27-48) 3-6 months post-dose 3, 25 % (-2-45) > 6 months post-dose 3, and 30 % (-6-54) ≥ 14 days post-dose 4. CONCLUSIONS: Booster doses initially provided high protection against BA.5 at a level similar to that against BA.1/BA.2. However, the protection seemed shorter-lasting against BA.5, which likely contributed to the surge. Furthermore, rVE post-dose 4 was low even among recent vaccinees. These results support the introduction of variant-containing vaccines and emphasize the need for vaccines with longer duration of protection.

Three-dimensional CT cavernosography: reconsidering venous ligation surgery on the basis of the modern technology.

OBJECTIVE: • To examine the feasibility of three-dimensional (3D) CT cavernosography in the diagnosis of corporal veno-occlusive dysfunction. PATIENTS AND METHODS: • The subjects were 55 patients who had failed to respond to phosphodiesterase type 5 inhibitors. We performed pharmacodynamic infusion cavernosometry and cavernosography, using 60 mg papaverine hydrochloride. • Cavernosography was performed at 90 mmHg intracavernous pressure, using a multi-slice CT scan system. The 3D images were reconstructed using aquarius net station, ver.2 computer software. • For comparison with conventional cavernosography, maximum intensity projection (MIP) images were used. A flow of 20 mL/min or being more capable of maintaining 90 mmHg of intracavernous pressure indicated veno-occlusive dysfunction. RESULTS: • Forty-five of the 55 patients were diagnosed with corporal veno-occlusive dysfunction. 3D-CT cavernosography revealed drainage veins in all 45 cases, including cavernous veins, dorsal veins, crural veins and other emissary veins. • Compared with 3D-CT cavernosography, observing cavernous veins and the proximal part of the deep dorsal veins using MIP imaging was especially difficult because the origins of the penile veins are often behind the pelvic bone or cavernous body. • Of the patients who seemingly had leakage via the deep dorsal vein, 80.6% did not in fact have leakage via this vein, but had other leakages. The image resolution of 3D-CT cavernosography was significantly higher than that of MIP. CONCLUSION: • 3D-CT cavernosography can provide high-resolution images of venous drainage from any angle. We conclude that the images obtained by 3D-CT cavernosography are very helpful for both the diagnosis of corporal veno-occlusive dysfunction and the anatomical study of the human penile venous system.

Virtual cavernoscopy: a novel diagnostic tool for use in the corpus cavernosal lumen in patients with erectile dysfunction.

OBJECTIVE: • To evaluate virtual cavernoscopy as a diagnostic tool in erectile dysfunction. PATIENTS AND METHODS: • Forty patients who visited our hospital for investigation of erectile dysfunction underwent cavernosography using three-dimensional (3D)-computed tomography (CT). • Virtual cavernoscopic images were reconstructed from 3D-CT data. RESULTS: • Virtual cavernoscopic images were obtained from all patients. • Virtual cavernoscopy visualized the corpus cavernosal lumen surrounded by the tunica albuginea, the septum of the cavernosum, the outlets of the veins, and cavernous arteries. • The visualization of each structure depended on the window level (WL). At WL 400, the virtual cavernoscopy visualized only a fibrous structure. At this WL, the internal view of the corpus cavernosum was expressed as a hollow space. At WL 1600, the virtual cavernoscopy visualized the cavernous artery as a filling defect. • Out of 80 lumens in the 40 subjects, arteries in 14 lumens were detected by both virtual cavernoscopy and CT angiography, while arteries in 50 lumens were detected only by virtual cavernoscopy. Arteries in two lumens could not be visualized by either method and those in 14 lumens were visualized only by CT angiography. CONCLUSION: • In visualizing the artery, conventional imaging techniques depend on blood flow, whereas using virtual cavernoscopy an artery can be visualized independently of blood flow. Virtual cavernoscopy is unique in this regard and we therefore believe that this new imaging technology will contribute to better ED practice.

Variations of the internal pudendal artery as a congenital contributing factor to age at onset of erectile dysfunction in Japanese.

OBJECTIVE: To investigate the relationship between variations of the pelvic artery arrangement and the age at erectile dysfunction (ED) onset, as some men develop ED while relatively young, while others maintain erectile function into old age despite having cardiovascular diseases, thus congenital factors might be involved. PATIENTS AND METHODS: We examined 290 units of internal iliac arteries (IIA) in 145 patients showing repeated incomplete erectile response to intracavernosal injections with prostaglandin E(1). Patients with cardiovascular risk factors, neurological disease or pelvic injury were excluded. The pelvic artery arrangement, evaluated by three-dimensional computed tomographic angiography, was classified anatomically into five types: Type 1 (normal or basic type), in which the internal pudendal artery (IPA) originates from the anterior trunk at the level between the linea terminalis and the major ischial notch; Type 2, the IPA originates from the anterior trunk of the IIA at the level of the major ischial notch or more distally; Type 3, the IPA originates directly from the IIA at a level proximal to the linea terminalis; Type 4, the IPA originates together with the superior and inferior gluteal artery within 1 cm of each other; and Type 5, the penile blood supply is dependent on arteries other than the IPA, such as the obturator artery. RESULTS: Among the 290 units, eight could not be classified due to poor image quality. There were no statistically significant differences in blood flow parameters among the types of IIAs, but there was a statistically significant difference in the IPA type at the age of onset of ED. Type 1 (153 units or 53%) anatomy, was more common in patients who developed ED at an advanced age. Types 2, 3 and 4 were more common in patients with onset of ED at an early age (log-rank test P < 0.001, P = 0.044, P < 0.001, respectively). Compared with patients with the common type of IIAs bilaterally, patients with any of the variations bilaterally are at risk of early onset of ED (log-rank test: P = 0.002). CONCLUSION: In these anatomical studies, nearly half of all internal artery units are variations in type. Congenital factors might contribute to the development of ED. If a man has bilateral variation from the common type (Type 1), he might develop ED approximately 10 years earlier than those who are identical in every way except for their IPA (Type 1) arrangements.

Effect of aldosterone on isolated human penile corpus cavernosum tissue.

OBJECTIVE: To clarify the physiological effects of aldosterone on human penile corpus cavernosum (hPCC) tissue, as aldosterone has a wider physiological action than just the maintenance of electrolyte balance, and there are mineralocorticoid receptors, i.e. aldosterone receptors, in hPCC tissue. MATERIALS AND METHODS: Specimens of hPCC were obtained from 10 patients (mean age 38 years, range 21-75), with informed consent and approval by the local ethics committee. One patient had a penectomy because of penile cancer, and nine had a penile biopsy because of erectile dysfunction. Patients with diabetes mellitus, hypertension or ischaemic heart disease were excluded. In a pharmacological study we evaluated the effect of aldosterone on the isolated hPCC tissues. RESULTS: Aldosterone caused no significant change in resting tension and did not affect the nitric oxide-dependent relaxation reaction. However, the dose-response curve of noradrenaline was shifted to the left when the strip preparation was treated with aldosterone (1 x 10(-5)M) for 20 min before administering noradrenaline. Moreover, the shift to the left was completely blocked when spironolactone (anti-aldosterone agent) was added as a pre-treatment. Pre-treatment with aldosterone also significantly extended the mean (SEM) time required to reach 50% relaxation of a noradrenaline-induced contraction, of 9.3 (1.5) min, vs the control, of 5.2 (1.0) min (P = 0.002). CONCLUSION: Aldosterone has no direct contractile action or a relaxant action on human penile cavernous tissue, but acts to significantly enhance the noradrenaline-induced contraction. The effect on the noradrenaline-induced contraction is probably caused by aldosterone enhancing the affinity of the alpha-receptors for noradrenaline in hPCC. We suggest that aldosterone acts to enhance contraction of hPCC tissue, and is one of the restraining factors for human penile erection.

Markers in peritoneal effluent for withdrawal from peritoneal dialysis: multicenter prospective study in Japan.

The most serious problem in peritoneal dialysis (PD) is the risk of final complication by encapsulating peritoneal sclerosis (EPS) because of peritoneal deterioration. Markers useful for the noninvasive evaluation ofperitoneal deterioration are therefore required. In this multicenter prospective study of stable PD patients, we compared the dialysate-to-plasma (D/P) concentration ratios of albumin, immunoglobulin G, and c2-macroglobulin, and effluent levels of interleukin 6 (IL-6) and fibrinogen/fibrin degradation products (FDPs) to clarify the relationship between inflammation, fibrinolysis markers, and permeability to large molecules. At the beginning of the present study, significantly positive correlations were noted between the IL-6 and FDP concentrations and the D/P ratios of albumin and a2-macroglobulin. In addition, a significantly positive correlation was noted between the FDP and IL-6 concentrations. However, the D/P ratio of creatinine obtained by peritoneal equilibration test did not positively correlate with those markers. Moreover, a significantly positive correlation was noted between changes in the effluent concentrations of FDPs and IL-6 and in permeability markers for large molecules. The effluent IL-6 and FDP concentrations reflect a chronic inflammatory state in the peritoneum, which is associated with increased permeability to large molecules. In individual PD patients, careful observation of the clinical course and evaluation of changes in such markers are expected to predict peritoneal deterioration and the development of EPS.

Penile revascularization surgery for arteriogenic erectile dysfunction: the long-term efficacy rate calculated by survival analysis.

OBJECTIVE: To determine the subjective and objective outcomes (by survival analysis) after penile revascularization surgery in patients with arteriogenic erectile dysfunction (ED), selected by established strict criteria. PATIENTS AND METHODS: The study included 51 patients diagnosed with arteriogenic ED caused by localised arterial lesions and who had microscopic penile revascularization surgery between January 1996 and March 2002. Before surgery, all patients had a full examination, including a medical and sexual history, laboratory testing, intracavernosal pharmacological tests, colour Doppler ultrasonography (CDU), pharmacodynamic infusion cavernosometry and cavernosography, and digital subtraction angiography (DSA). Penile revascularization surgery was indicated only in patients aged <50 years and with no history of diabetes mellitus, hypertension or hyperlipidaemia. When there were communicating branches between the dorsal and cavernosal arteries, Hauri's procedure was used; when there were none or there was no evidence for them on both CDU and DSA because of severe narrowing or obstruction in the proximal common penile artery, the Furlow-Fisher modification of the Virag V procedure (FFV5) was used. The patency of the neo-arterial blood flow was assessed by CDU and effective rates calculated using the Kaplan-Meier method. The efficacy rate was recalculated whenever there was a recurrence. When occlusion of the neo-arterial blood was confirmed by CDU the date of occlusion was set as that midway between the last examination showing patency of the donor vessel and the latest examination indicating the occlusion. The patency period was the number of days from surgery to the date of occlusion. RESULTS: Of the 51 patients, 26 had Hauri's and 23 the FFV5 procedure (median age 32 years, range 21-49); in two patients with a previous pelvic fracture surgery was not possible because of scar formation in the dorsal area at the base of the penis. The mean (sd) subjectively estimated efficacy rate was 85.9 (6.3)% after 3 and 67.5 (10.7)% after 5 years of follow-up. The duration at 75% efficacy was 41.0 (5.6) months. The objectively estimated efficacy rate was 84.9 (7.3)% at 3 and 65.5 (13.5)% after 5 years of follow-up. The duration at 75% patency was 42.4 (9.5) months, and at 50% was 60.6 (19.4) months. There was no significant difference in subjective outcome between the FFV5 and Hauri procedures (P = 0.38, log rank test) and none objective outcome after surgery (P = 0.19, log rank test). Thirteen of the 18 patients in the Hauri group had venous dilatation in the deep dorsal, obturator, prostatic and the internal iliac veins. There were operative complications in four patients (hyperaemia of the glans in two, and one each with haemorrhage from the anastomosis site and scar contracture). CONCLUSIONS: The long-term efficacy rates (by the Kaplan-Meier method) of the Hauri and FFV5 procedures were both acceptable. The selection criteria gave acceptable outcomes from both procedures. Penile revascularization surgery is a treatment suitable only for young men and therefore attention must be given not only to the long-term outcome but also to long-term adverse events.