Outcome of surgical parathyroidectomy for tertiary hyperparathyroidism in kidney transplant recipients: tertiary hyperparathyroidism should not be ignored, for the sake of precious allografts.

Tertiary hyperparathyroidism is a complication of kidney transplantation. This complicated condition carries over from the dialysis period and varies according to the function of the transplanted allograft. Treatments include pharmacotherapy (mainly using calcimimetics) and parathyroidectomy, but calcimimetics are currently not covered by the national insurance system in Japan. Two types of parathyroidectomy can be performed: subtotal parathyroidectomy; and total parathyroidectomy with partial autograft. Both types can be expected to improve hypercalcemia. Concerns about the postoperative deterioration of allograft function are influenced by preoperative allograft function, which is even more likely to be affected by early surgery after kidney transplantation. In general, transient deterioration of allograft function after surgery is not expected to affect graft survival rate in the medium to long term. Tertiary hyperparathyroidism in kidney transplant recipients negatively impacts allograft and patient survival rates, and parathyroidectomy can be expected to improve prognosis in both kidney recipients and dialysis patients. However, studies offering high levels of evidence remain lacking.

Secondary normal pressure hydrocephalus following pituitary apoplexy: A case report.

Background: Although secondary normal pressure hydrocephalus (sNPH) can occur in various central nervous system diseases, there are no reports of sNPH caused by pituitary lesions. Herein, we present a unique case of sNPH caused by pituitary apoplexy. Case Description: A 70-year-old man was transferred to our hospital because of a sudden onset of headache and loss of consciousness. The cerebrospinal fluid (CSF) test showed slightly elevated cell counts and protein levels but a negative CSF culture test. Magnetic resonance imaging showed a dumbbell-like cystic lesion with hemorrhagic change at the sella turcica. From the above, the patient was diagnosed with aseptic meningitis caused by pituitary apoplexy. Pituitary hormone replacement therapy was undertaken, and his symptoms fully improved. However, two months later, he complained of a gait disturbance and incontinence that had gradually appeared. Brain imaging with computed tomography showed no ventricular enlargement compared with initial images, although the lateral ventricles were slightly enlarged. As a CSF drainage test improved his symptoms temporarily, sNPH with possible longstanding overt ventriculomegaly in adults (LOVA) background was suspected. We performed a lumboperitoneal shunt (LPS) placement, which improved his symptoms. Conclusion: This case suggests that sNPH can develop even after a small subarachnoid hemorrhage caused by a pituitary apoplexy in LOVA patients. If the aqueduct of Sylvius is open, sNPH with a LOVA background can be successfully treated with LPS placement.

Negative impact of ratio of the microvascular area to tumor area on the response to EGFR-TKI in non-small cell lung cancer with an EGFR mutation.

Background: The clinical impact of tumor microvessels on the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) in EGFR mutation-positive non-small cell lung cancer (NSCLC) is unclear. Thus, the aim of this study was to investigate whether a tumor microenvironment, abundant in microvessels, affects EGFR-TKI efficacy in patients with NSCLC and EGFR mutations. Methods: We retrospectively studied the data of 40 post-operative patients with recurrent NSCLC and EGFR mutations who received EGFR-TKIs as a first-line treatment at Kumamoto University Hospital from January 2010 to February 2021. Tumor sections were retrieved from the tissue registry and analyzed for CD34-positive microvessels using immunohistochemical techniques. The ratio of microvascular area to tumor area (RMV), which is the CD34-positive microvascular area compared to the total tumor area, was measured using StrataQuest. The predictive value of RMV on treatment outcome, assessed via progression-free survival (PFS), was evaluated using a multivariate Cox proportional hazard model. Results: The median PFS in the high RMV group (≥0.058) was significantly shorter than that in the low RMV group [<0.058; 296 days, 95% confidence interval (CI): 217-374 vs. 918 days, 95% CI: 279-1,556, P=0.002]. Multivariate analysis revealed that high RMV was an independent negative predictor of PFS (hazard ratio, 3.21; 95% CI: 1.18-8.76, P=0.022). Conclusions: High RMV may critically affect EGFR-TKI resistance in patients with NSCLC and EGFR mutations.

[Case of a Patient with Cancer of Unknown Primary in the Poor Prognosis Group Who Had a Experienced a Beneficial Treatment Course].

A 47-year-old woman with general malaise and abdominal pain presented with multiple liver tumors and lymph node metastasis. She was diagnosed with small cell carcinoma on the basis of a lymph node biopsy; however, the primary lesion was not identified. Finally, we diagnosed her with cancer of unknown primary lesion and placed her in the poor prognosis group. Although her general condition was poor, she experienced a relatively good response to treatment for small cell carcinoma.

Cell-free DNA methylation profile potential in the diagnosis of lung squamous cell carcinoma.

Background: Aberrant methylation plays an essential role in early cancer development. In this study, we investigated methylation patterns in lung squamous cell carcinoma (LUSC) and matched non-tumor tissue and plasma samples to evaluate the potential of these patterns in the diagnosis of LUSC. Methods: The study group included 49 patients with stage I-III LUSC. We collected resected tumor tissue, paired peritumoral tissue, distant normal tissue, and corresponding plasma samples. A bespoke lung cancer bisulfite sequencing panel was used to profile the methylation level. Another 48 healthy volunteers provided control plasma samples. Results: Peritumoral and distant normal tissues presented similar methylation signatures, distinct from those in tumor tissue samples. A comparison of methylation profiles led to the identification of 871 tumor-specific differentially methylated blocks, including 847 hypermethylated and 24 hypomethylated blocks (adjusted P value <0.05). All top-ranked blocks were tumor-related. Tissue samples were analyzed for field cancerization to identify progressively aggravating aberrant methylations during tumor initiation and development. The analysis revealed that 221 blocks presented a stepwise increase in methylation levels, while seven blocks presented a stepwise decrease in methylation pattern as the sampling drew nearer to the tumor. The malignant contaminated ratio (MCR) confirmed the presence of distinct methylation patterns between tumor and peritumoral tissue samples. We then constructed a diagnostic panel using a combined diagnostic score of cell-free DNA (cfDNA) that showed high sensitivity and specificity. The healthy controls had a significantly lower combined diagnostic score (cd-score) than LUSC patients. Additionally, based on the methylation profiles, LUSC could be classified into two subgroups, C1 and C2. The methylation profile of the C2 group was not distinct from the healthy controls, which had a significantly lower cd-score than did the C1 group. Conclusions: LUSC-specific methylation patterns could potentially discriminate between peritumoral tissue, distant normal tumor tissue, and tumor tissues. This preliminary study also supported the potential utility of cfDNA methylation analysis in diagnosing LUSC.

The impact of factor Xa inhibitors on bleeding risk in patients with respiratory diseases.

It is unclear which factor Xa (FXa) inhibitors are associated with higher bleeding risk in patients with respiratory diseases, and there are no studies on the association between prothrombin time-international normalized ratio (PT-INR) and bleeding risk. We conducted a retrospective cohort study comparing 1-year-outcomes and PT-INR between patients with respiratory diseases treated with rivaroxaban (R group, n = 82) or edoxaban (E group, n = 138) for atrial fibrillation or venous thromboembolism from 2013 to 2021. The most frequent event of all bleeding discontinuations was respiratory bleeding in both groups (7.3 and 4.3%, respectively). The cumulative incidence of bleeding discontinuation was significantly higher in the R group (25.6%) than in the E group (14.4%) (hazard ratio [HR], 2.29; 95% confidence interval [CI] 1.13-4.64; P = 0.023). PT-INR after initiation of therapy significantly increased and was higher in the R group than in the E group (median value, 1.4 and 1.2, respectively; P < 0.001). Multivariate analysis using Cox proportional hazards and Fine-Gray models revealed that PT-INR after initiation of therapy was an independent risk factor of bleeding discontinuation events (HR = 4.37, 95% CI 2.57-7.41: P < 0.001). Respiratory bleeding occasionally occurs in patients receiving FXa inhibitors, and monitoring the PT-INR may need to ensure safety.

Subcortical hemorrhage caused by cerebral amyloid angiopathy compared with hypertensive hemorrhage.

OBJECTIVES: Most published reports on lobular hemorrhage in cerebral amyloid angiopathy (CAA) include patients diagnosed only by imaging studies. This study analyzed patients with subcortical hemorrhage histologically diagnosed as CAA or non-CAA (hypertensive). METHODS: This is a retrospective study analyzing data from 100 craniotomy cases. Tissue of hematoma cavity wall was collected for histological investigation in hematoma removal by surgery in patients with subcortical hemorrhage. Statistical analyses of blood pressure, hematoma location and volume, outcome, and mortality was performed in CAA and non-CAA groups. RESULTS: There were 47 CAA and 53 non-CAA cases, and average age was significantly older in the CAA group (p < 0.01). Blood pressure was significantly lower (p < 0.01) but hematoma volume was significantly greater (p < 0.05) in the CAA group. Rebleeding occurred in two CAA cases and one non-CAA case, but no re-operations were required. Average score of modified Rankin Scale, which is used to measure the degree of disability in patients who have had a stroke, at three months after surgery was not significantly different between the two groups (CAA: 3.94 ± 1.28, non-CAA: 3.58 ± 1.50). There were seven deaths in the CAA and six in the non-CAA group, and intraventricular hemorrhage highly complicated in the death cases in both groups. In the CAA group, average age of the fatal cases was significantly older than that of the surviving cases (p < 0.05) and six cases demonstrated dementia before onset of hemorrhage. CONCLUSIONS: Surgical removal of a subcortical hemorrhage caused by CAA is not contraindicated. However, age > 80 years, complication with intraventricular hemorrhage, hematoma volume ≥ 50 ml, and dementia before onset of hemorrhage contribute to high mortality, and craniotomy should be carefully considered for such patients. A limitation of this study is that comparison between CAA and non-CAA groups was performed in the patients with only surgically indicated ICH, and does not evaluate entire ICH cases with CAA. However, this study appropriately compared pathologically diagnosed CAA and non-CAA in patients with moderate to severe lobular ICH with surgical indications.

Targeting N-Myristoylation Through NMT2 Prevents Cardiac Hypertrophy and Heart Failure.

Protein diversity can increase via N-myristoylation, adding myristic acid to an N-terminal glycine residue. In a murine model of pressure overload, knockdown of cardiac N-myristoyltransferase 2 (NMT2) by adeno-associated virus 9 exacerbated cardiac dysfunction, remodeling, and failure. Click chemistry-based quantitative chemical proteomics identified substrate proteins of N-myristoylation in cardiac myocytes. N-myristoylation of MARCKS regulated angiotensin II-induced cardiac pathological hypertrophy by preventing activations of Ca2+/calmodulin-dependent protein kinase II and histone deacetylase 4 and histone acetylation. Gene transfer of NMT2 to the heart reduced cardiac dysfunction and failure, suggesting targeting N-myristoylation through NMT2 could be a potential therapeutic approach for preventing cardiac remodeling and heart failure.

Midline Shift Induced by the Drainage of Cerebrospinal Fluid in Three Patients With External Decompression.

It is not rare that progressive hydrocephalus worsens clinical conditions in a patient with external decompression and drainage or shunt surgery is required. However, spinal drainage or shunt surgeries potentially carry a risk of causing paradoxical herniation in a patient with decompressive craniectomy, particularly in a comatose case with wide craniectomy. Careful and strict observations are necessary for such patients. In our three comatose cases with craniectomy, paradoxical herniation occurred due to excessive drainage after 5-7 days of shunt surgery and lumbar drainage, although the drainage pressure was set at more than 10 cmH2O. Fortunately, in the three cases, the herniation improved within a few days after the drain was clamped and the bed was flattened. However, the Trendelenburg position and epidural blood patch might be necessary if paradoxical herniation occurs acutely after lumbar puncture or drainage because delayed resolution can be fatal in the herniation.

Initial experience of transpapillary gallbladder biopsy using newly designed device delivery system.

Transpapillary gallbladder biopsy has been reported for the diagnosis of gallbladder disease, and this procedure requires special biopsy forceps or a large-diameter pusher catheter. We retrospectively examined consecutive patients who underwent transpapillary gallbladder biopsy using a newly designed device delivery system (Endosheather; Piolax Medical Device, Kanagawa, Japan). We evaluated 11 patients (median age, 71 years [28-85]) who underwent transpapillary gallbladder biopsy from June 2021 to July 2022. The selective gallbladder cannulation and delivery system insertion success rate was 90.9% (10/11). The target lesion biopsy success rate was 63.6% (7/11). The biopsy time (i.e., time to completion of biopsy after successful guidewire placement) was 8.7 (5.4-32.7) min. In 1 patient in whom all 6 gallbladder bile juice cytology results were benign, the biopsy result was suspicious of adenocarcinoma. The final diagnosis for this patient was gallbladder cancer. Adverse events occurred in 2 patients. In 1 patient, acute cholecystitis occurred and required emergency surgery. Transpapillary gallbladder biopsy using the Endosheather is a potential option for the diagnosis of gallbladder disease. A good indication for this technique is considered to be wall thickening at the gallbladder fundus, where it is difficult to differentiate between benign and malignant lesions by imaging modalities such as ultrasonography or endoscopic ultrasound. The addition of transpapillary gallbladder biopsy may be advantageous when performing bile juice cytology using a nasogallbladder drainage tube for the diagnosis of gallbladder disease.

Clinical factors associated with acute abdominal symptoms induced by gastric anisakiasis: a multicenter retrospective cohort study.

BACKGROUND: Gastric anisakiasis typically causes severe abdominal symptoms; however, we incidentally detected asymptomatic gastric anisakiasis cases during esophagogastroduodenoscopy. The factors associated with developing acute abdominal symptoms induced by gastric anisakiasis remain unclear. Therefore, this study aimed to investigate the clinical factors associated with abdominal symptoms of gastric anisakiasis by comparing symptomatic and asymptomatic cases. METHODS: This was a retrospective cohort study involving 264 patients diagnosed with gastric anisakiasis at nine hospitals in Japan between October 2015 and October 2021. We analyzed patients' medical records and endoscopic images and compared the clinical factors between the symptomatic and asymptomatic groups. RESULTS: One hundred sixty-five patients (77.8%) were diagnosed with abdominal symptoms, whereas 47 (22.2%) were asymptomatic. Older age, male sex, diabetes mellitus, gastric mucosal atrophy, and gastric mucosal atrophy of the Anisakis penetrating area were significantly more common in the asymptomatic group than in the symptomatic group. Multivariate analysis revealed that age (p = 0.007), sex (p = 0.017), and presence or absence of mucosal atrophy (p = 0.033) were independent factors for the occurrence of acute abdominal symptoms. In addition, cases that were Helicobacter pylori naïve, with an elevation of white blood cells, or without an elevation of eosinophils were more common in the symptomatic group than in the asymptomatic group. CONCLUSIONS: Age, sex, and presence or absence of gastric mucosal atrophy were the clinical factors associated with the occurrence of acute abdominal symptoms. Older and male patients and those with gastric mucosal atrophy were less likely to show abdominal symptoms. The mechanisms of the occurrence of symptoms induced by gastric anisakiasis remain unclear; however, our results will help clarify this issue in the future.

Adult Infratentorial Pial Arteriovenous Fistula Treated with Detachable Coils: A Case Report and a Review of Literature.

An appropriate therapeutic option for pial arteriovenous fistula (PAVF) can vary according to the angioarchtecture of the lesion. We present a case of adult infratentorial PAVF treated by transarterial coil embolization. A 26-year-old man was referred to our institution for an asymptomatic intracranial vascular lesion. Cerebral angiograms revealed PAVF fed by three arteries in the right cerebellomedullary cistern. The feeding arteries were accurately identified by three-dimensional rotational angiography and were successfully embolized using coils while normal arterial flow was preserved. This case report suggests that stepwise transarterial coil embolization can cure PAVF under detailed evaluation of its angioarchitecture.

Clinical complete response maintained for more than 5 years after aggressive chemoradiotherapy for advanced rectal cancer with necrotizing fasciitis: a case report.

We report the case of a 65-year-old male diagnosed with advanced rectal cancer associated with necrotizing fasciitis (NF). Since radical surgery, total pelvic exenteration with sacrectomy, was rejected because of detrimental effects on quality of life, chemoradiotherapy (CRT) was chosen as anti-cancer treatment after urgent debridement. Although CRT was paused unintentionally just after delivering the total dose of radiation owing to the relapse of NF, the patient has maintained clinical complete response (cCR) without any distant metastasis for >5 years. Advanced rectal cancer is recognized as an NF risk factor. No definitive treatment strategies have been reported for NF-inducing rectal cancer; however, some reports have demonstrated curative extended surgery. Thus, CRT may be a less-invasive treatment option for NF-inducing rectal cancer, whereas severe adverse effects including re-infection after debridement should be closely monitored.

Tumor steatosis and glutamine synthetase expression in patients with advanced hepatocellular carcinoma receiving atezolizumab plus bevacizumab therapy.

AIM: The anti-programmed death-ligand 1 antibody atezolizumab and vascular endothelial growth factor-neutralizing antibody bevacizumab in combination (Atezo + Bev) have become the first-line therapy in advanced hepatocellular carcinoma (HCC). Distinct types of tumor immune microenvironment (TIME) and their associations with specific molecular subclasses and driver gene mutations have been identified in HCC; however, these insights are mainly based on surgically resected early-stage tumors. The current study aimed to reveal the biology and TIME of advanced HCC and their significance in predicting clinical outcomes of Atezo + Bev therapy. METHODS: Thirty-three patients with advanced HCC who were scheduled for treatment with Atezo + Bev therapy were included in this study. Pretreatment tumor biopsy, pre- and posttreatment diffusion-weighted magnetic resonance imaging (MRI) with nine b values (0-1500 s/mm2 ), and other clinicopathologic factors were analyzed. RESULTS: Compared with resectable HCC, advanced HCC was characterized by higher proliferative activity, a higher frequency of Wnt/ß-catenin-activated HCC, and lower lymphocytic infiltration. Prognostically, two metabolism-related factors, histopathologically determined tumor steatosis and/or glutamine synthetase (GS) expression, and MRI-determined tumor steatosis, were the most significant prognostic indicators for progression-free survival (PFS) and overall survival after Atezo + Bev therapy. Furthermore, changes in the pre- and posttreatment true diffusion coefficients on MRI, which might reflect changes in TIME after treatment, were significantly associated with better PFS. CONCLUSIONS: The biology and TIME of HCC were strikingly different in advanced HCC compared with those of surgically resected HCC. Two metabolism-related factors, pathologically determined tumor steatosis and/or GS expression, and MRI-determined tumor steatosis, were found to be the most significant prognostic indicators for Atezo + Bev therapy in advanced HCC.

Prognostic Role of Circulating LTBP-2 in Patients With Dilated Cardiomyopathy: A Novel Biomarker Reflecting Extracellular Matrix LTBP-2 Accumulation.

BACKGROUND: Dilated cardiomyopathy (DCM) is a life-threatening disease related to heart failure. Extracellular matrix proteins have an important role in the pathogenesis of DCM. Latent transforming growth factor beta-binding protein 2 (LTBP-2), a type of extracellular matrix protein, has not been investigated in DCM. METHODS: First, we compared plasma LTBP-2 levels in 131 patients with DCM who underwent endomyocardial biopsy and 44 controls who were matched for age and sex and had no cardiac abnormalities. Next, we performed immunohistochemistry for LTBP-2 on endomyocardial biopsy specimens and followed the DCM patients for ventricular assist device (VAD) implantation, cardiac death, and all-cause death. RESULTS: Patients with DCM had elevated plasma LTBP-2 levels compared with controls (P < 0.001). Plasma LTBP-2 levels were positively correlated with LTBP-2-positive fraction in the myocardium from the biopsy specimen. When patients with DCM were divided into 2 groups according to LTBP-2 levels, Kaplan-Meier analysis demonstrated that patients with high plasma LTBP-2 were associated with increased incidences of cardiac death/VAD and all-cause death/VAD. In addition, patients with high myocardial LTBP-2-positive fractions were associated with increased incidences of these adverse outcomes. Multivariable Cox proportional hazard analysis showed that plasma LTBP-2 and myocardial LTBP-2-positive fraction were independently associated with adverse outcomes. CONCLUSIONS: Circulating LTBP-2 can serve as a biomarker to predict adverse outcomes, reflecting extracellular matrix LTBP-2 accumulation in the myocardium in DCM.

Syntheses and Structures of Arenethiolato Cobalt(II) Complexes Containing Acylamino Groups: Steric Effects of Bulky Ligands on Coordination and Geometry.

Bulky thiolato ligands have been developed for creating biomimetic model complexes of active sites in metalloenzymes. Herein, we report a series of di-ortho-substituted arenethiolato ligands containing bulky acylamino groups (RCONH; R = t-Bu-, (4-t-BuC6H4)3C-,{3,5-(Me2CH)2C6H3}3C-, and {3,5-(Me3Si)2C6H3}3C-) that were developed for biomimetics. Bulky hydrophobic substituents generate a hydrophobic space around the coordinating sulfur atom through the NHCO bond. This steric environment induces the formation of low-coordinate mononuclear thiolato Co(II) complexes. The well-positioned NHCO moieties in the hydrophobic space coordinate to the vacant sites of the cobalt center with different coordination modes, viz., the S,O-chelate of the carbonyl C═O or the S,N-chelate of the acylamido CON-. The solid (crystalline) and solution structures of the complexes were investigated in detail using single-crystal X-ray crystallography, 1H NMR, and absorption spectroscopic analyses. The spontaneous deprotonation of NHCO, which is commonly observed in metalloenzymes but requires a strong base in artificial systems, was simulated by forming a hydrophobic space in the ligand. This new ligand design strategy is advantageous for creating model complexes that have never been constructed artificially.

Questionnaire survey on pharmacists' roles among non- and health care professionals in medium-sized cities in Japan.

Although the scope of pharmacists' work has expanded in Japan, people's perception of this is unclear. To contribute to medical care together with non- and health care professionals, clarifying the perceptions of these groups is important to best utilize pharmacist professionals. We conducted a cross-sectional questionnaire survey among non-health care professionals (n = 487) and nurses (n = 151), medical doctors (n = 133), and pharmacists (n = 204) regarding the work of pharmacists. The questionnaire comprised 56 items in four categories associated with the roles of pharmacists. For each questionnaire item, we performed logistic regression analysis to compare pharmacists' opinions with those of other professionals and non-health care professionals. Opinions were similar between pharmacists and nurses or medical doctors regarding "collecting patient information" and "providing drug information to patients." However, there were differences in perceptions regarding "medical collaboration" (nurses; 8/23 items, physicians; 11/23 items) and "community medicine" (nurses; 9/15 items, physicians; 11/15 items), and pharmacists themselves perceived greater roles related to health care collaboration and community health care. Perceptions of non-health care professionals were poorer than those of pharmacists in all categories (47/56 items). These results suggest that pharmacists must actively communicate to help others understand their specialty and build trusting relationships to improve patient care.

Lynch syndrome-associated chordoma with high tumor mutational burden and significant response to immune checkpoint inhibitors.

Chordoma is a rare malignant bone tumor arising from notochordal tissue. Conventional treatments, such as radical resection and high-dose irradiation, frequently fail to control the tumor, resulting in recurrence and re-growth. In this study, genetic analysis of the tumor in a 72-year-old male patient with refractory conventional chordoma of the skull base revealed a high tumor mutational burden (TMB) and mutations in the MSH6 and MLH1 genes, which are found in Lynch syndrome. The patient and his family had a dense cancer history, and subsequent germline genetic testing revealed Lynch syndrome. This is the first report of a chordoma that has been genetically proven to be Lynch syndrome. Chordomas usually have low TMB; however, this is an unusual case, because the TMB was high, and immune checkpoint inhibitors effectively controlled the tumor. This case provides a basis for determining the indications for immunotherapy of chordoma based on the genetic analysis. Therefore, further extensive genetic analysis in the future will help to stratify the treatment of chordoma.

Effect of Mammalian Target of Rapamycin Inhibition on Activated Regulatory T-Cell Expansion in Kidney Transplantation.

BACKGROUND: The mammalian target of rapamycin (mTOR) plays a critical role in the host immune response in organ transplantation. This study evaluates the regulatory benefits of mTOR inhibitors in kidney transplant recipients (KTRs). METHODS: The mTOR-dependent immune-regulating effects in KTRs were evaluated by examining T-cell subsets among peripheral blood mononuclear cells from 79 KTRs. Recipients included an early introduction of everolimus (EVR) and reduced-exposure tacrolimus group (n = 46) and a standard tacrolimus-based without EVR (non-EVR) group (n = 33). RESULTS: Trough concentrations of tacrolimus at 3 months and 1 year were significantly lower in the EVR group than the non-EVR group (both P < .001). In addition, the respective proportions of patients without estimated glomerular filtration rate < 20% in the EVR and non-EVR groups were 100% and 93.3% at 1 year, 96.3% and 89.7% at 2 years, and 96.3% and 89.7% at 3 years after blood collection, respectively (P = .079). The frequencies of CD3+ T cells and CD4+ T cells among peripheral blood mononuclear cells were comparable between groups. Total CD25highCD127-CD4+ regulatory T (Treg) cells were similar in the EVR and non-EVR groups. In contrast, circulating CD45RA-CD25highCD127-CD4+ activated Treg cells were significantly higher in the EVR group (P= .008). CONCLUSION: These results suggest that the early introduction of mTOR benefits long-term kidney graft function and circulating activated Treg-cell expansion in KTRs.

A Unique Case of Intracranial Amelanotic Melanoma with BRAF V600E Mutation Successfully Treated via Molecular-targeted Therapy.

Melanoma carries a high risk of brain metastasis. A small subset of metastatic melanomas, known as amelanotic melanomas, does not present black coloration, reflecting a lack of melanin pigmentation. Here, we report a case of B-Raf proto-oncogene (BRAF) V600E mutation associated with a metastatic brain tumor caused by the amelanotic melanoma. A 60-year-old man was transferred to our department following acute onsets of left upper limb paralysis and convulsion. In the brain imaging, multiple lesions in the right frontal lobe and left basal ganglia were detected, and the presence of an enlarged left axillary lymph node was revealed. Consequently, we removed the right frontal lesion and performed a biopsy of the left axillary lymph node. Histological analysis of both specimens indicated an amelanotic melanoma, and genetic testing revealed a BRAF V600E mutation. The residual intracranial lesions were treated with stereotactic radiotherapy and molecular-targeted therapy, with dabrafenib and trametinib as the systemic treatment. Based on the Response Evaluation Criteria in Solid Tumors, we determined that the patient achieved complete remission (CR) under uninterrupted molecular-targeted therapy over a period of 10 months. After the temporary withdrawal of dabrafenib and trametinib to avoid hepatic dysfunction, a new intracranial lesion appeared. CR of this lesion was achieved following reinstatement of the two drugs. These results suggest that, under limited conditions, molecular-targeted therapy can produce a sustained response against the intracranial metastasis of melanoma, and the therapy with reduced dose is still effective against a recurrent case after cessation of the therapy due to the toxicity.