Long-lasting renal dysfunction following tacrolimus induction therapy in ulcerative colitis patients

Although tacrolimus (TAC) has remarkable effects in ulcerative colitis (UC) patients when given as remission induction therapy, some can develop renal dysfunction during TAC administration, resulting in withdrawal, though related details remain poorly understood. This study was conducted to determine the impact of oral TAC on renal function for remission induction therapy in UC patients. Fifty-five patients (10 elderly, 45 non-elderly) with UC and treated with oral TAC at our hospital were retrospectively evaluated. Renal function was assessed using estimated glomerular filtration rate (eGFR). Although a high clinical response to TAC was seen in both elderly and non-elderly, a decline in eGFR was noted in nearly all patients regardless of age, with a maximum change of −34.4% from the baseline value at week 11. Furthermore, eGFR decline recovered quickly after TAC discontinuation, though did not return to the baseline at two years following cessation. The rate of eGFR change at week 12 was significantly associated with patient age (β = −0.3242, p = 0.0103) and peak serum trough level during TAC treatment (β = 0.3563, p = 0.0051). Furthermore, the rate of decline in eGFR was significantly greater during treatment with TAC in the elderly as compared to non-elderly, with a large difference in eGFR decline rate between those groups also noted at two years after withdrawal of treatment. Careful attention to renal function when administering oral TAC for UC is important and changes in eGFR should be monitored closely in elderly patients even after treatment cessation.     

Phase IIb study of pembrolizumab combined with S‐1 + oxaliplatin or S‐1 + cisplatin as first‐line chemotherapy for gastric cancer

The KEYNOTE‐659 study evaluated the efficacy and safety of first‐line pembrolizumab plus S‐1 and oxaliplatin (SOX) (cohort 1) or S‐1 and cisplatin (SP) (cohort 2) for advanced gastric/gastroesophageal junction (G/GEJ) cancer in Japan. Herein, we update the results of cohort 1 and describe the results of cohort 2. This open‐label phase IIb study enrolled patients with advanced programmed death‐ligand 1 (PD‐L1)‐positive (combined positive score ≥ 1) human epidermal growth factor receptor 2 (HER2)‐negative G/GEJ adenocarcinoma. The primary end‐point was the objective response rate (ORR). Other end‐points were duration of response (DOR), disease control rate (DCR), progression‐free survival (PFS), overall survival (OS), and safety. One hundred patients were enrolled. In cohorts 1 and 2, median follow‐up time was 16.9 and 17.1 months; ORR (central review), 72.2% and 80.4%; DOR, 10.6 and 9.5 months; DCR (central review), 96.3% and 97.8%; median PFS (central review), 9.4 and 8.3 months; and median OS, 16.9 and 17.1 months, respectively. Treatment‐related adverse events (TRAEs) occurred in all patients, including peripheral sensory neuropathy (94.4%, cohort 1), decreased neutrophil count (82.6%, cohort 2), nausea (59.3% and 60.9% in cohorts 1 and 2), and decreased appetite (61.1% and 60.9% in cohorts 1 and 2). Grade 3 or higher TRAEs were reported by 59.3% (cohort 1) and 78.3% (cohort 2), including decreased platelet count (14.8%, cohort 1) and decreased neutrophil count (52.2%, cohort 2). Pembrolizumab in combination with SOX or SP showed favorable efficacy and safety in patients with PD‐L1‐positive, HER2‐negative G/GEJ adenocarcinoma.     

Biological evaluation on glass ionomer cement.

Biological properties of a new dental cement of glass ionomer cement were compared with other types of conventional cement. The biological test was carried out by tissue culture method and animal examination. The culture cells showed weaker reaction to the glass ionomer cement than zinc oxide-eugenol or polycarboxylate cement. Pulp tissue reaction showed no significant difference between glass ionomer and zinc oxide-eugenol cement from in vivo experiments using monkeys.     

The Simultaneous Onset of Pancreatitis and Colitis as Immune-related Adverse Events in a Patient Receiving Nivolumab Treatment for Renal Cell Carcinoma

Immune checkpoint inhibitors (ICIs), which have anti-tumor effects, are currently approved for treatment of several kinds of advanced malignancies. However, with their increasing use, a variety of immune-related adverse events (irAEs) in administered patients have been reported. We herein report a rare case of the simultaneous onset of acute pancreatitis and colitis as irAEs during nivolumab treatment given to a patient with renal cell carcinoma, who then shown marked improvement with corticosteroid therapy.     

Repeated Necrotizing Lymphadenitis with MEFV Gene Mutations

We herein report a 36-year-old man with repeated necrotizing lymphadenitis due to MEFV gene mutations. The patient''s chief complaints were a fever and painful cervical lymphadenopathy. We diagnosed him with necrotizing lymphadenitis based on the pathological findings of the lymph nodes and the exclusion of other differential diseases. The same episode recurred four times. We speculated the involvement of autoinflammatory backgrounds and detected MEFV gene mutations of E148Q (homo), P369S, and R408Q. Considering the elevation of interleukin-18, these mutations probably played roles in the repeated necrotizing lymphadenitis.     

Erk pathways negatively regulate matrix mineralization

Skeletal mineralization is an important step regulating the mechanical properties of the calcified tissues, but molecular events underlying mineralization still remain elusive. We examined the role of extracellular signal-regulated kinase (Erk) pathways in matrix mineralization of osteogenic cells both in vitro and in vivo. Matrix mineralization by preosteocytic MLO-A5 cells and osteoblastic MC3T3-E1 cells was increased by either PD98059 Mek inhibitor treatment or adenovirus vector-mediated dominant negative Ras (Ras(DN)) expression and was suppressed by Erk activation by platelet-derived growth factor (PDGF) treatment or constitutively active Mek1 (Mek(CA)) expression. Administration of adenovirus vectors carrying Ras(DN) gene onto the calvaria of 1-day-old mice increased the mineralization of the tissues, while that of the Mek(CA) adenovirus suppressed it. These results suggest that the Erk pathway is a negative regulator of the matrix mineralization both in vitro and in vivo.     

A case of retroperitoneal hemangiopericytoma

We report a case of a huge retroperitoneal tumor in a 67-year-old woman. When the patient was taken to another hospital by ambulance, she had lost consciousness because of hypertension and hypoglycemia and abdominal CT revealed a huge retroperitoneal tumor with deviation of the right kidney and inferior vena cava. After further examinations including ultrasonography, MRI and angiography in our hospital, the tumor was extirpated. The tumor, 22 x 17 x 10 cm in size and 2,580 g in weight was diagnosed as hemangiopericytoma histologically. She has remained well with no evidence of recurrence for 9 months since the operation.     

Flumazenil antagonizes midazolam-induced airway narrowing during nasal breathing in humans

We measured nasal resistance (Rn) while awake, during midazolam-induced sedation and after antagonism with flumazenil (n = 9). Nasal and oral airflow were measured. Rn was calculated by dividing the difference between maximal nasal mask and oropharyngeal pressures by inspiratory airflow at minimum pharyngeal pressure. During sedation, two subjects developed obstructive apnoeic events and four subjects had snoring events. Each apnoea was ended by mechanisms other than a change in breathing route. After antagonism with flumazenil, apnoeic and snoring events were abolished. Rn during midazolam sedation (median 1.46 (25th percentile 1.00, 75th 2.61) kPa litre-1 s) was significantly greater than before midazolam (0.29 (0.25, 0.48) kPa litre-1 s) and after flumazenil (0.41 (0.25, 0.58) kPa litre-1 s) (P < 0.01 in each subject). We conclude that midazolam increased Rn, sometimes leading to obstruction, and flumazenil abolished this increase in Rn.      

Protective effect of nisoldipine on myocardial ischemia during coronary bypass surgery.

BACKGROUND: Nisoldipine, a calcium antagonist, was assessed for myocardial protection and the prevention of reperfusion injury in patients undergoing CABG. METHODS: Of the 34 subjects undergoing CABG in this study, 20 were given nisoldipine orally at 10 mg/day for 2 weeks before surgery (N group) and the other 14 untreated controls (C group). Myocardial protection was conducted via ante-grade cold blood cardioplegia at 20-minute intervals. RESULTS: Myocardial blood flow was significantly higher in the N group (67.8 +/- 21.8 ml/100 g vs. 47.2 +/- 14.4 ml/100 g, p < 0.05) after cardiopulmonary bypass. Serum interleukin-6 levels were significantly lower in the N group 1 hour after reperfusion (116 +/- 58 vs. 409 +/- 362 pg/ml, p < 0.05), as were serum lactate dehydrogenase levels immediately after surgery (888 +/- 268 vs. 1350 +/- 486 IU/L, p < 0.05). The N Group showed a better left ventricle stroke work index 6 hours after surgery (43 +/- 8 vs. 36 +/- 9 g.m/m2). Dopamine dosage in the N group on postoperative day 1 was lower than in controls (5.3 +/- 1.9 vs. 3.0 +/- 2.4 micrograms/kg/min). CONCLUSIONS: Preoperative nisoldipine treatment increased blood flow in the postischemic myocardium and prevented myocardial damage and reperfusion injury to some extent.     

Interobserver variation in diagnosis of dementia by brain perfusion SPECT

Brain perfusion SPECT (BP-SPECT) has characteristic patterns of abnormality, enabling the differential diagnosis of dementia. The purpose of this study was to measure interobserver variations in the diagnosis of dementia using BP-SPECT. BP-SPECT images of 57 cases, 19 of Alzheimer's disease (AD), eight of multi-infarct dementia (MID), three of Pick's disease, five of other dementias, and 22 normal controls, were interpreted by ten nuclear medicine physicians with varying levels of experience. Brain MR images of the cases were then interpreted apart from SPECT. The physicians independently rated all of the diagnoses listed beforehand according to a five-point scale, with clinical information provided. Receiver-operating characteristic (ROC) curves and the area under the ROC curve (Az) were calculated. Az varied from 0.48 to 0.87. Mean Az's were significantly larger (p<0.05) in the diagnosis by SPECT than in that by MRI (0.715 and 0.629 for dementia vs. normal, 0.670 and 0.560 for AD or MID vs. normal, 0.610 and 0.416 for AD vs. normal, and 0.672 and 0.412 for AD vs. MID, respectively). Considerable interobserver variation was present in BP-SPECT interpretation. BP-SPECT may be more effective for the evaluation of dementia than MRI when the same nuclear medicine physicians interpret both images.