Hong Kong consensus recommendations on the management of pancreatic ductal adenocarcinoma.

This project was undertaken to develop the first set of consensus statements regarding the management of pancreatic ductal adenocarcinoma (PDAC) in Hong Kong, with the goal of providing guidance to local clinicians. A multidisciplinary panel of experts discussed issues surrounding current PDAC management and reviewed evidence gathered in the local context to propose treatment recommendations. The experts used the Delphi approach to finalise management recommendations. Consensus was defined as ≥80% acceptance among all expert panel members. Thirty-nine consensus statements were established. These statements cover all aspects of PDAC management, including diagnosis, resectability criteria, treatment modalities according to resectability, personalised management based on molecular profiling, palliative care, and supportive care. This project fulfils the need for guidance regarding PDAC management in Hong Kong. To assist clinicians with treatment decisions based on varying levels of evidence and clinical experience, treatment options are listed in several consensus statements.

National prevalence and socioeconomic factors associated with the acceptance of COVID-19 vaccines in South Korea: a large-scale representative study in 2021.

OBJECTIVE: Among the global efforts toward preventing the COVID-19 pandemic, vaccines are a pivotal factor in ending the pandemic. Thus, through a large-scale population-based study, we investigated the individual-, social-, and family-associated factors affecting the acceptance of COVID-19 vaccines in South Korea. PATIENTS AND METHODS: Data were obtained from a nationwide representative study (Korea Community Health) conducted in 2021. To determine the individual-, social-, and family-associated variables for COVID-19 vaccination acceptance, we investigated data from 225,319 individuals. RESULTS: In the total sample (n=225,319), 184,529 COVID-19-vaccinated people and 40,790 non-vaccinated people were evaluated. The factors related to the acceptance of COVID-19 vaccination were significantly associated with the demographic factors, namely, older age group, female sex, and a history of influenza vaccination, as well as medical conditions such as diabetes, hypertension, and depression. Socioeconomic conditions influencing the acceptance of COVID-19 vaccination were significantly associated with low-income families and blue-collar workers. Health-related risk factors were high in the obese group. However, a noteworthy negative association was found between the acceptance of vaccination and smoking habits and alcohol consumption. Conversely, a positive association was observed between academic level and vaccination acceptance. CONCLUSIONS: Our findings suggest that old age, female sex, a history of influenza vaccination, medical conditions, such as diabetes, hypertension, and depression, low-income families, blue-collar workers, and health-related risk factors, such as obesity, were associated with the acceptance of COVID-19 vaccination. Additionally, a high academic level, absence of smoking habits, and non-current alcohol use were positively associated with vaccine acceptance.

Oxford hip and knee scores deteriorate in patients awaiting lower limb arthroplasty during the COVID-19 pandemic and predict a health state 'worse than death'.

The COVID-19 pandemic has caused unprecedented disruption to elective orthopaedic services. The primary objective of this study was to examine changes in functional scores in patients awaiting total hip arthroplasty (THA), total knee arthroplasty (TKA), and unicompartmental knee arthroplasty (UKA). Secondary objectives were to investigate differences between these groups and identify those in a health state 'worse than death' (WTD). In this prospective cohort study, preoperative Oxford hip and knee scores (OHS/OKS) were recorded for patients added to a waiting list for THA, TKA, or UKA, during the initial eight months of the COVID-19 pandemic, and repeated at 14 months into the pandemic (mean interval nine months (SD 2.84)). EuroQoL five-dimension five-level health questionnaire (EQ-5D-5L) index scores were also calculated at this point in time, with a negative score representing a state WTD. OHS/OKS were analyzed over time and in relation to the EQ-5D-5L. A total of 174 patients (58 THA, 74 TKA, 42 UKA) were eligible, after 27 were excluded (one died, seven underwent surgery, 19 non-responders). The overall mean OHS/OKS deteriorated from 15.43 (SD 6.92), when patients were added to the waiting list, to 11.77 (SD 6.45) during the pandemic (p < 0.001). There were significantly worse EQ-5D-5L index scores in the THA group (p = 0.005), with 22 of these patients (38%) in a health state WTD, than either the TKA group (20 patients; 27% WTD), or the UKA group (nine patients; 21% WTD). A strong positive correlation between the EQ-5D-5L index score and OHS/OKS was observed (r = 0.818; p < 0.001). Receiver operating characteristic analysis revealed that an OHS/OKS lower than nine predicted a health state WTD (88% sensitivity and 73% specificity). OHS/OKS deteriorated significantly among patients awaiting lower limb arthroplasty during the COVID-19 pandemic. Overall, 51 patients were in a health state WTD, representing 29% of our entire cohort, which is considerably worse than existing pre-pandemic data.

Risk factors for delirium among patients with advanced cancer in palliative care: a multicenter, patient-based registry cohort in South Korea.

OBJECTIVE: Previous studies have comprehensively investigated the prevalence and various potential risk factors for delirium among patients with advanced cancer admitted to the acute palliative care unit (APCU). Our objective was to evaluate the comprehensive association between delirium and various risk factors among patients with advanced cancer in an acute palliative care setting using a patient-based multicenter registry cohort. PATIENTS AND METHODS: We performed a multicenter, patient-based registry cohort study collected in South Korea between January 1, 2019, and December 31, 2020. Delirium was identified using a medical record review based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. RESULTS: In total, 2,124 eligible patients with advanced cancer in the APCU met the inclusion criteria. There were 127 out of 2,124 patients (prevalence, 6.0%; 95% CI, 5.0 to 7.1) with delirium during admission. Delirium in patients with advanced cancer was associated with age >70 years (OR, 1.793; 95% CI, 1.246 to 2.581), male sex (OR, 1.675; 95% CI, 1.131 to 2.479), no chemotherapy during hospitalization (OR, 2.019; 95% CI, 1.236 to 3.298), hearing impairment (OR, 3.566; 95% CI, 1.176 to 10.810), underweight (OR, 1.826; 95% CI, 1.067 to 3.124), current use of opioid medication (OR, 1.942; 95% CI, 1.264 to 2.982), previous history of delirium (OR, 12.497; 95% CI, 6.920 to 22.568), and mental illness (OR, 2.333; 95% CI, 1.251 to 4.352). CONCLUSIONS: In a large-scale multicenter patient-based registry cohort, delirium was associated with old age, male sex, no chemotherapy during hospitalization, hearing impairment, underweight, current use of opioid medication, and a history of delirium and mental illness. Our findings suggest physicians should pay attention to delirium in patients with advanced cancer admitted to the APCU with the above risk factors.

Neuropsychological adverse drug reactions of Remdesivir: analysis using VigiBase, the WHO global database of individual case safety reports.

OBJECTIVE: Although remdesivir (GS-5734) has recently demonstrated clinical benefits against the pandemic outbreak of coronavirus disease 2019 (COVID-19), neuropsychological adverse reactions (ADRs) remain to be examined in real-world settings. Therefore, we aimed to identify and characterize the neuropsychological ADRs associated with remdesivir use. MATERIALS AND METHODS: We obtained data for this international pharmacovigilance cohort study from individual case safety reports (ICSRs) in a World Health Organization database (VigiBase) from the first report on remdesivir on February 17, 2020, until August 30, 2020 (n=1,403,532). ADRs reported to be relevant to remdesivir were compared with the full database by using a Bayesian neural network method to calculate the information component (IC). RESULTS: A total of 2,107 reported cases of neuropsychological ADRs suspected to be associated with remdesivir were identified from among all ICSRs in the database during the observation period. Although 108 neuropsychological ADRs (64 neurologic events and 44 psychologic events) were reported in association with the medication, no statistically significant pharmacovigilance signal could be detected; the IC025 value was negative for all of the neuropsychological dysfunctions (anxiety [n=13, 0.62%], seizures [n=12, 0.57%], lethargy [n=6, 0.28%], agitation [n=5, 0.25%], cerebral infarction [n=3, 0.14%], ischemic stroke [n=3, 0.14%], and hemiparesis [n=3, 0.14%]). CONCLUSIONS: Our study demonstrates that remdesivir, a novel drug applied to the treatment of COVID-19, does not have a significant association with adverse neurologic or psychiatric reactions in the real-world setting.

Efficacy and safety of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) monotherapy for advanced EGFR-mutated non-small cell lung cancer: systematic review and meta-analysis.

OBJECTIVE: It is controversial whether there is efficacy or safety benefit of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) in advanced EGFR-mutated non-small cell lung cancer (NSCLC) compared to standard chemotherapy. We aim to assess the efficacy and safety of EGFR-TKIs compared to other chemotherapeutics in EGFR-mutated NSCLC. MATERIALS AND METHODS: Up to April 27th, 2020, PubMed, Embase, Medline, Scopus, Cochrane library, and ClinicalTrials.gov were searched for articles or trials meeting the inclusion criteria. After filtering, 230 eligible studies were initially identified. Data extraction followed PRISMA and included outcomes were progression-free survival (PFS), overall survival (OS), and severe adverse events (SAEs). Direct and indirect meta-analyses were generated in the context of log-linear mixed-effects models, with fixed effects for each relative comparison and random effects for each study. RESULTS: The results showed that EGFR-TKI therapy had improved PFS with a hazard ratio (HR) of 0.40 (95% CI: 0.36-0.44, p<0.001) compared to standard chemotherapy. Nevertheless, the EGFR-TKIs showed no benefit on OS (HR: 0.96, 95% CI: 0.83-1.10, p=0.556). In the analysis of adverse events, EGFR-TKIs had fewer SAEs than standard chemotherapy (HR: 0.29, 95% CI: 0.26-0.33, p<0.001). CONCLUSIONS: Our systemic review indicates that EGFR-TKI therapy has improved PFS, and reduced SAEs compared to standard chemotherapy in advanced EGFR-mutated NSCLC.

Reversible cerebral vasoconstriction syndrome: a comprehensive systematic review.

OBJECTIVE: We aimed to analyze clinical characteristics, treatment patterns, and prognosis of patients with reversible cerebral vasoconstriction syndrome (RCVS). MATERIALS AND METHODS: Two investigators independently searched PubMed and EMBASE, and 191 cases were included in this study. Information regarding demographics, triggering factors, brain imaging findings, treatment modalities, recurrence, and clinical outcome was collected. RESULTS: The mean age of the patients was 39.9 years, and 155 (81.2%) were female. The most common triggering factor for RCVS was an exposure to vasoactive substances (41.4%), followed by pregnancy/postpartum (20.9%), and sexual intercourse (10.5%). Multifocal stenosis (84.0%) and beading shape (82.4%) were the leading abnormal findings on angiography, while cerebral ischemic lesions (47.6%) and cerebral hemorrhage (mainly subarachnoid hemorrhage) (35.1%) were the main findings on brain computed tomography (CT)/magnetic resonance imaging (MRI). Calcium channel blockers (nimodipine/verapamil) were the most commonly used medications (44.5%) in the treatment of RCVS. Multivariate analysis identified that RCVS was precipitated by trauma/surgery/procedure (hazard ratio (HR): 3.29, 95% confidence interval (CI) (1.21-8.88), p=0.019), and presence of aphasia/neglect/apraxia during the acute phase of the disease (HR: 3.83, 95% CI (1.33-11.05), p=0.013) were found to be the two independent risk factors for residual neurological deficit after RCVS. CONCLUSIONS: In our systematic review, vasoactive substances were the most frequent triggers for RCVS, which was most commonly accompanied by angiographic findings of multifocal stenotic lesions. Patients with RCVS precipitated by trauma or surgical procedures and those with focal cortical deficits had a higher risk of residual neurological deficits, and these patients should closely be monitored.

FoxO1 as a Regulator of Aquaporin 5 Expression in the Salivary Gland.

Forkhead box O1 (FoxO1) is a multifunctional initiator, mediator, and repressor of autoimmune diseases in an organ- or disease-specific manner. However, the role of FoxO1 in the salivary gland has not yet been elucidated. In this study, we discovered that FoxO1 and aquaporin 5 (AQP5) are both significantly downregulated in the patients with primary Sjögren syndrome, an autoimmune disease accompanying salivary gland dysfunction. Pharmacologic or genetic perturbation of FoxO1 in the rat salivary gland acinar cell line, SMG-C6, induced a significant downregulation of AQP5 expression, as observed in clinical specimens. There was a strong correlation between FoxO1 and AQP5 expression because FoxO1 is a direct regulator of AQP5 expression in salivary gland acinar cells through its interaction with the promoter region of AQP5. Serial injection of a FoxO1 inhibitor into mice induced a reduction of AQP5 expression in submandibular glands and, consequently, hyposalivation, which is one of the major clinical symptoms of primary Sjögren syndrome. However, there was no sign of inflammation or cell damage in the submandibular glands harvested from mice treated with the FoxO1 inhibitor. In conclusion, our findings indicate that FoxO1 in salivary gland tissue acts as a direct regulator of AQP5 expression. Thus, downregulation of FoxO1 observed in primary Sjögren syndrome is a putative mechanism for hyposalivation without the involvement of previously reported soluble factors in primary Sjögren syndrome patient sera.

Risk factors of COVID-19 mortality: a systematic review of current literature and lessons from recent retracted articles.

OBJECTIVE: Recently, two influential articles that reported the association of (hydroxy)chloroquine or angiotensin converting enzyme (ACE) inhibitors and coronavirus disease 2019 (COVID-19) mortality were retracted due to significant methodological issues. Therefore, we aimed to analyze the same clinical issues through an improved research method and to find out the differences from the retracted papers. We systematically reviewed pre-existing literature, and compared the results with those of the retracted papers to gain a novel insight. MATERIALS AND METHODS: We extracted common risk factors identified in two retracted papers, and conducted relevant publication search until June 26, 2020 in PubMed. Then, we analyzed the risk factors for COVID-19 mortality and compared them to those of the retracted papers. RESULTS: Our systematic review demonstrated that most demographic and clinical risk factors for COVID-19 mortality were similar to those of the retracted papers. However, while the retracted paper indicated that both (hydroxy)chloroquine monotherapy and combination therapy with macrolide were associated with higher risk of mortality, our study showed that only combination therapy of hydroxychloroquine and macrolide was associated with higher risk of mortality (odds ratio 2.33; 95% confidence interval 1.63-3.34). In addition, our study demonstrated that use of ACE inhibitors or angiotensin receptor blockers (ARBs) was associated with reduced risk of mortality (0.77; 0.65-0.91). CONCLUSIONS: When analyzing the same clinical issues with the two retracted papers through a systematic review of randomized controlled trials and relevant cohort studies, we found out that (hydroxy)chloroquine monotherapy was not associated with higher risk of mortality, and that the use of ACE inhibitors or ARBs was associated with reduced risk of mortality in COVID-19 patients.

Malignant Peripheral Nerve Sheath Tumour in the Urinary Bladder of a Dog.

A 15-year-old neutered male miniature pinscher was presented with a pedunculated mass (4 × 1 cm) in its urinary bladder. Exploratory cystotomy revealed that the mass was located at the trigone of the bladder and projected into the lumen. The cut surface of the mass was homogeneous grey to tan in colour with focal brown pigmentation. Microscopically, the mass was predominantly composed of neoplastic spindle cells characterized by moderate cellular pleomorphism, invasion into the muscular layer of the bladder wall and few mitotic figures. The neoplastic spindle cells formed interwoven bundles intersecting at various angles. Immunohistochemically, these cells were negative for cytokeratin 7 and α-smooth muscle actin, but strongly expressed S100 and vimentin, confirming a diagnosis of a malignant peripheral nerve sheath tumour (PNST). To the best of our knowledge, this is the first report of a primary malignant PNST in the urinary bladder of a dog.

Dissolution enhancement of sorafenib tosylate by co-milling with tetradecanol post-extracted using supercritical carbon dioxide.

Sorafenib (SOR) is an important multikinase inhibitor for the treatment of cancers. It is commercially available (Nexavar from Bayer) in the form of sorafenib tosylate (SORt) due to its very low solubility. Studies have been made to further improve the dissolution behavior of the tosylate form (SORt), which could ultimately moderate the currently high daily dose. In the present study, SORt nanoparticles (SORt-NP) were prepared through a process that combined two industrially well-accepted techniques of co-milling and supercritical extraction. SORt was co-milled with hydrophilic polymers and tetradecanol, and the tetradecanol was post-extracted using supercritical carbon dioxide. The process enabled the formation of SORt-NP without using any toxic organic solvents, and the drug/excipient ratio (1:0.38) was substantially higher than determined in other studies (1:5.4-10). The enhanced dissolution behavior of SORt-NP was possible with an optimized number of milling cycles. Combining co-milling and supercritical extraction was able to form overall porous network structures with reduced crystallite size, which accelerated the dissolution of SORt-NP. The current method could be easily extended to other poorly soluble drugs as a general approach to improve their dissolution behaviors.

An IFN-γ and TNF-α dual release fluorospot assay for diagnosing active tuberculosis.

OBJECTIVES: Currently available interferon (IFN)-γ-release assays (IGRA) cannot discriminate active tuberculosis (TB) from latent TB infection (LTBI), and so have limited clinical utility for diagnosing active TB. Since numbers of tumour necrosis factor (TNF)-α-producing T cells are highly correlated with active TB, we hypothesized that detecting IFN-γ- and/or TNF-α-producing T cells would overcome this limitation of IGRA. This study evaluated the diagnostic performances of the IFN-γ and TNF-α dual release fluorospot assay for active TB. METHODS: Adult patients with suspected TB including recent TB exposers were prospectively enrolled over a 28-month period. In addition to the conventional IGRA test (i.e. QuantiFERON-In-Tube), a fluorospot assay for detecting IFN-γ- and TNF-α-producing T cells was performed. The final diagnoses were classified by clinical category. Patients with confirmed or probable TB were regarded as active TB, and patients with not active TB were further classified as having not active TB with and without LTBI, based on the QuantiFERON-In-Tube results. RESULTS: A total of 153 patients including 45 with active TB and 108 with not active TB (38 LTBI vs. 70 not LTBI) were finally analysed. The sensitivity and specificity of the QuantiFERON-In-Tube assay for active TB were 84% (95% confidence interval (CI), 70-93) and 70% (95% CI 61-79), respectively. The IFN-γ/TNF-α dual release assay by fluorospot had substantially higher diagnostic specificity (94%) for diagnosing active TB than the IFN-γ single release assay (72%, p < 0.001), without compromising sensitivity (84% vs. 89%, p 0.79). CONCLUSIONS: The fluorospot-based IFN-γ/TNF-α dual release assay appears to be a simple and useful test for diagnosing active TB.

Detection of Local Recurrence in Patients with Head and Neck Squamous Cell Carcinoma Using Voxel-Based Color Maps of Initial and Final Area under the Curve Values Derived from DCE-MRI.

BACKGROUND AND PURPOSE: Early detection of local recurrence is important to increase the chance of cure because local recurrence is the main cause of treatment failure in head and neck squamous cell carcinoma. We evaluated the added value of voxel-based color maps of dynamic contrast-enhanced MR imaging compared with conventional MR imaging alone for detecting local recurrence of head and neck squamous cell carcinoma. MATERIALS AND METHODS: We retrospectively enrolled 63 consecutive patients with head and neck squamous cell carcinoma after definitive treatment and posttreatment surveillance MR imaging studies that demonstrated focal enhancement at the primary site. Three independent readers assessed conventional MR imaging and a pair of color maps of initial and final 90-second time-signal intensity areas under the curve from dynamic contrast-enhanced MR imaging. The sensitivities, specificities, and accuracies of both conventional MR imaging alone and combined interpretation of conventional and dynamic contrast-enhanced MR imaging were assessed using the clinicopathologic diagnosis as the criterion standard. κ statistics were used to evaluate interreader agreement. RESULTS: There were 28 patients with subsequently documented local recurrence and 35 with posttreatment change. Adding dynamic contrast-enhanced MR imaging to conventional MR imaging significantly increased the diagnostic accuracies for detecting local recurrence (48%-54% versus 87%-91%; P < .05), with excellent interreader agreement (κ = 0.8; 95% CI, 0.67-0.92 to κ = 0.81; 95% CI, 0.69-0.93). By all 3 readers, the specificities were also significantly improved by adding dynamic contrast-enhanced MR imaging to conventional MR imaging (22%-43% versus 87%-91%; P < .001) without sacrificing the sensitivities (68%-82% versus 86%-89%; P > .05). CONCLUSIONS: Adding voxel-based color maps of initial and final 90-second time-signal intensity areas under the curve from dynamic contrast-enhanced MR imaging to conventional MR imaging increases the diagnostic accuracy to detect local recurrence in head and neck squamous cell carcinoma by improving the specificity without sacrificing the sensitivity.

The role of 18F-fluciclovine PET in the management of prostate cancer: a systematic review and meta-analysis.

AIM: To investigate the diagnostic performance of 18F-fluciclovine positron-emission tomography (PET) or combined PET and computed tomography (PET/CT) for diagnosis of primary cancer, preoperative lymph node (LN) staging, and detection of recurrent disease of prostate cancer (PCa) through a systematic review and meta-analysis. MATERIALS AND METHODS: The PubMed and EMBASE databases were searched from the earliest available date of indexing through 31 December 2018, for studies evaluating the diagnostic performance of 18F-fluciclovine PET or PET/CT for the management of PCa patients. The sensitivities, specificities, and positive and negative likelihood ratios (LR+ and LR-) across the studies were calculated and summary receiver operating characteristic curves were constructed. RESULTS: Across 13 studies (563 patients), the pooled sensitivity for 18F-fluciclovine PET or PET/CT for diagnosis of primary PCa was 0.87 (95% confidence interval [CI]: 0.77-0.93) and a pooled specificity of 0.84 (95% CI: 0.68-0.93). For LN staging, the pooled sensitivity was 0.56 (95% CI: 0.37-0.74) and a pooled specificity of 0.98 (95% CI: 0.88-1.00). For detection of recurrent disease, the pooled sensitivity was 0.79 (95% CI: 0.60-0.91) and a pooled specificity of 0.69 (95% CI: 0.59-0.77). In meta-regression analysis, no definite variable was the source of the study heterogeneity. CONCLUSION: The current meta-analysis showed the moderate sensitivity and specificity of 18F-fluciclovine PET or PET/CT for the diagnosis of primary cancer, preoperative LN staging, and detection of recurrent PCa. Further large multicentre studies will be necessary to substantiate the diagnostic accuracy of 18F-fluciclovine PET/CT for management of PCa patients.

Temporal evaluation of the microwave ablation zone and comparison of CT and gross sizes during the first month post-ablation in swine lung.

PURPOSE: The purpose of this study was to investigate the development and evolution of the microwave ablation (MWA) lesion in the normal lung by using a swine model at various time points and to compare post-procedural computed tomography (CT) and gross pathologic findings during the first month post-ablation. MATERIALS AND METHODS: Twenty-seven percutaneous MWA procedures were performed on swine lungs at 100W for either 2min (low dose, 18 ablations) or 10min (high dose, 9 ablations). Animals were sacrificed at either 2 days (n=5) or 28 days (n=5) after ablation. All animals underwent CT imaging immediate post-treatment and prior to sacrifice, with additional imaging at 7 and 14 days for the 28-day cohort. After euthanasia, lungs and trachea were removed en bloc and underwent gross pathology analysis. RESULTS: In both dose treatment groups, CT measurements of the ablation zone were maximum at Day 7 (low dose: 7.50±3.08 cm3; high dose: 24.87±11.34 cm3) and significantly larger compared to the immediate post-ablation measurements (low dose: 2.54±1.81 cm3; P=0.00011; high dose: 9.14±3.42 cm3; P=0.00374). No significant differences in dimensions were observed between CT and gross pathologic images for both high and low dose ablations in both cohorts. CONCLUSION: The treatment zone following MWA in the lung can vary in the sub-acute setting, achieving largest size at 7 days post-treatment. Furthermore, measurements from CT closely matched with gross pathologic ablation size.

Confluent and reticulated papillomatosis: Case series of 3 patients from Kedah, Malaysia and literature review.

Confluent and reticulated papillomatosis (CRP) was first described in 1927 by Gougerot and further characterised by Carteud.1 It is relatively rare, and the exact pathophysiology was not well known. Over the years, multiple treatment modalities were proposed. We report our experience with three cases of CRP which showed complete clearance with tetracycline group of antibiotics.

Effect of Low-Dose Vs Standard-Dose Valganciclovir in the Prevention of Cytomegalovirus Disease in Kidney Transplantation Recipients: A Systemic Review and Meta-Analysis.

BACKGROUND: Valganciclovir is widely used to prevent post-transplant cytomegalovirus (CMV) infection in kidney transplant patients. However, the currently used dose remains controversial because the continuous use of this drug decreases kidney function and can induce leukopenia. OBJECTIVE: The purpose of this study was to measure the appropriate dose of valganciclovir required to prevent CMV infection. METHODS: A systematic review and meta-analysis were performed by using a random effects model. The Cochrane Central Register, MEDLINE, EMBASE, and PubMed databases were searched up to April 15, 2017. We conducted analysis on low-dose (450 mg) and standard-dose (900 mg) valganciclovir groups. RESULTS: After completion of the research, the analysis revealed that the glomerular filtration rate, graft loss, tacrolimus level, antibody-mediated rejection, and fungal and Candida infection rates did not differ between the 2 groups. However, the incidence of CMV tended to decrease in the low-dose group (0.584 [95% confidence interval [CI], 0.352-0.967]; P = .036). The biopsy-proven rejection rate decreased by 0.427 times in the low-dose group compared with the standard-dose group (95% CI, 0.274-0.667; P = .002). Furthermore, the incidence of leukopenia decreased by 0.371 times in the low-dose group compared with the standard-dose group (95% CI, 0.264-0.523; P = .001). CONCLUSIONS: The 450-mg dose of valganciclovir effectively prevented post-transplantation CMV infection and decreased drug-induced side effects such as leukopenia. In the future, the lower dose of valganciclovir should be considered to prevent CMV infection and enhance cost-effectiveness.

High-Dose Intravenous Immunoglobulin Treatment of Polyomavirus Nephropathy Developing After T Cell-Mediated Rejection Treatment: A Case Report.

BACKGROUND: Reactivation of BK polyomavirus causes destructive virus allograft nephropathy; however, treatment options are limited. Herein, we report a case in which a patient with T cell-mediated rejection was treated with steroid therapy. The patient subsequently developed BK viremia and was successfully treated by using intravenous immunoglobulin (IVIG) after failing to respond to conventional treatment. CASE PRESENTATION: A 54-year-old man had been undergoing peritoneal dialysis for 3 years before kidney transplantation. He had an elevated serum creatinine level (2.26 mg/dL; normal range, 1.2-1.4 mg/dL) and reduced urine output 2 months after transplantation. Suspecting T cell-mediated rejection, steroid pulse therapy (methylprednisolone 250 mg twice daily) was performed for 3 days. Despite treatment, there was a recurrence of increased serum creatinine, and real-time quantitative polymerase chain reaction (serum samples) indicated BK viremia (>5.5 × 105 copies/mL). Results of a kidney biopsy revealed polyomavirus nephropathy (BK virus positive and C4d negative). Thus, the patient's tacrolimus dosage was reduced (from 2.75 mg twice daily to 2 mg once daily), he discontinued mycophenolate mofetil, and he was administered ciprofloxacin and leflunomide. However, the BK viremia showed no improvement, even after 3 months of treatment. Thus, he was administered high-dose IVIG (1 g/kg, 5 times over 5 weeks). The viremia load (blood specimen) decreased to 5197 copies/mL, and the patient's graft function stabilized. His serum creatinine decreased to 2.68 mg/dL. The patient is currently being followed up. CONCLUSIONS: Optimal BK treatment methods have not been established, and IVIG treatment remains controversial. However, the present case provides an example of successful treatment using high-dose IVIG.

Voltage-dependent Ca2+ channels promote branching morphogenesis of salivary glands by patterning differential growth.

Branching morphogenesis is a crucial part of early developmental processes in diverse organs, but the detailed mechanism of this morphogenic event remains to be elucidated. Here we introduce an unknown mechanism leading to branching morphogenesis using mouse embryonic organotypic cultures with time-lapse live imaging. We found spatially expressed L-type voltage-dependent Ca2+ channels (VDCCs) in the peripheral layers of developing epithelial buds and identified the VDCCs as a core signaling mediator for patterning branching architecture. In this process, differential growth in peripheral layers by VDCC-induced ERK activity promoted cleft formation through an epithelial buckling-folding mechanism. Our findings reveal an unexpected role of VDCCs in developmental processes, and address a fundamental question regarding the initial process of branching morphogenesis.

Graft Contrast-Induced Nephropathy Caused by Prerenal Transplant Computed Tomography: A Case Report.

BACKGROUND: We report a case of posttransplant contrast-induced nephropathy (CIN) that occurred after performing computed tomography (CT) scanning for pretransplant cardiac and vascular evaluation. CASE PRESENTATION: The patient had an 8-year history of hemodialysis and was admitted to the hospital for a kidney transplant from a deceased donor. Cardiac CT imaging and 3-dimensional low-extremity CT angiography were performed to confirm the patient's cardiac and iliac artery function. After successful transplantation surgery, the patient had a urine output of 250 mL and a reduced creatinine level from 8.8 to 2.3 mg/dL on postoperative day 4. However, urine output suddenly decreased to 30 mL and the creatinine level suddenly increased to 7.6 md/dL without any symptoms such as fever or graft tenderness. The patient tested negative for panel-reactive antibodies and donor-specific antibodies, and he was discharged 1 week later with an improvement in symptoms. Results of a graft biopsy indicated CIN, and the contrast-enhanced kidney was observed on noncontrast CT imaging that was performed immediately after transplantation to rule out vascular problems as well as other complications. CONCLUSIONS: There may be residual contrast present from pretransplant CT imaging, which could affect the functional kidney grafts after transplantation and can lead to CIN. This scenario could potentially lead to loss of graft function, suggesting that caution should be observed when ordering CT imaging in this patient population.