Pembrolizumab-related Immune Thrombocytopenia in a Patient with Lung Adenocarcinoma Treated by Radiotherapy: Potential Immune-related Adverse Event Elicited by Radiation Therapy

The effect of radiotherapy during immunotherapy on immune-related adverse events (irAEs) is not fully understood. We herein report a 74-year-old woman diagnosed with lung adenocarcinoma with programmed death ligand 1 expression ≥50% and treated with pembrolizumab. She developed fatal immune thrombocytopenia associated with pembrolizumab immediately following radiotherapy. A flow cytometry analysis of peripheral blood detected an increased expression of programmed death-1 (PD-1) and Ki-67 in CD4^＋ and CD8^＋ T cells after radiotherapy, compared with pre-irradiation measurements. This case suggests that radiotherapy may evoke irAEs during treatment with anti-PD-1 antibodies, which physicians should consider when using radiotherapy in patients treated with these drugs.     

PAX5 alterations in an infant case of KMT2A‐rearranged leukemia with lineage switch

Lineage switch is a rare event at leukemic relapse. While mostly known to occur in KMT2A‐rearranged infant leukemia, the underlying mechanism is yet to be depicted. This case report describes a female infant who achieved remission of KMT2A‐MLLT3‐rearranged acute monocytic leukemia, but 6 months thereafter, relapsed as KMT2A‐MLLT3‐rearranged acute lymphocytic leukemia. Whole exome sequencing of the bone marrow obtained pre‐post lineage switch revealed two somatic mutations of PAX5 in the relapse sample. These two PAX5 alterations were suggested to be loss of function, thus to have played the driver role in the lineage switch from acute monocytic leukemia to acute lymphocytic leukemia.     

Prevention of surgical adhesions with gelatine sealing sheet in a canine adhesion model

Open in a separate window OBJECTIVESAlthough reoperation has been increasingly performed in cardiovascular surgery in recent years, preventing surgical adhesions remains an unsolved complication. Therefore, this study aimed to investigate whether gelatine sealing sheets are more effective than fibrin sealing sheets in preventing surgical adhesions.METHODSBilateral femoral arteries of 20 beagle dogs under general anaesthesia were pricked with syringe needles, and gelatine and fibrin sealing sheets were applied on the bleeding points to make canine adhesion models. The femoral artery was harvested after 4 and 12 weeks to evaluate adhesion formations. The adhesive grade was quantified by scoring the area and strength of adhesion tissues. Histological staining was performed to examine the structural features of surgical adhesions.RESULTSSignificantly fewer macroscopic adhesions were observed with gelatine sealing sheets than those with fibrin sealing sheets at 4 and 12 weeks postoperatively. Microscopically, CD3+ T lymphocytes at 4 and 12 weeks postoperatively in gelatine sealing sheets were significantly lower than those in fibrin sealing sheets. Microvessel density determined by CD34 at 4 and 12 weeks postoperatively in gelatine sealing sheets was also significantly lower than those in fibrin sealing sheets.CONCLUSIONSThe gelatine sealing sheets are more effective than the fibrin sealing sheets in preventing surgical adhesions. These findings suggest that the gelatine sealing sheet may help prevent adhesions and thus be a therapeutically effective biomaterial in vascular surgery.     

Genetically Diverse Highly Pathogenic Avian Influenza A(H5N1/H5N8) Viruses among Wild Waterfowl and Domestic Poultry,Japan, 2021

Genetic analyses of highly pathogenic avian influenza H5 subtype viruses isolated from the Izumi Plain, Japan, revealed cocirculation of 2 genetic groups of clade 2.3.4.4b viruses among migratory waterfowl. Our findings demonstrate that both continuous surveillance and timely information sharing of avian influenza viruses are valuable for rapid risk assessment.     

Comparison of Outcomes of Living and Deceased Donor Kidney Grafts Surviving Longer Than 5 Years in Korea

Background

It is generally recognized that living donor kidney transplantation (LDKT) grafts are superior to deceased donor kidney transplantation (DDKT) grafts. We compared survival and functional outcomes of LDKT and DDKT grafts.

Methods

Among 1000 kidneys transplanted from 1995 to 2008, we selected grafts surviving >5 years, excluding pediatric, multi-organ transplantation, and retransplantations (n = 454).

Results

There were 179 kidneys from deceased donors and 275 from living donors. Recipients showed no difference in age, gender, or cause of renal failure. Donors were younger in the DDKT group (30.6 vs 38.5 years; P < .05). There were more male donors in the DDKT group (73.2% vs 54.5%; P < .05). Deceased donors showed a greater mean number of HLA mismatches (4.2 vs 2.7; P < .05). Death-censored graft survival at 10 years showed no difference (DDKT 88.9% vs LDKT 88.9%; P = .99). Mean serum creatinine at 5 years was 1.41 mg/dL for DDKT and 1.44 mg/dL for LDKT (P = .75). Mean estimated glomerular filtration rate at 5 years was 67.8 mL/min/1.73 m² for DDKT and 62.1 mL/min/1.73 m² for LDKT (P = .23). Twenty-three DDKT grafts (12.8%) and 47 LDKT grafts (17.1%) experienced acute rejection episodes (P = .22). DDKT recipients showed more cases of viral and bacterial infections compared with LDKT recipients (viral, 11.7% vs 2.2% [P < .05]; bacterial, 21.8% vs 7.3% [P < .05]).

Conclusion

Among kidney grafts surviving >5 years, there was no difference in survival or serum creatinine levels at 5 and 10 years between DDKT and LDKT grafts.     

Donor Characteristics Associated With Reduced Survival of Transplanted Kidney Grafts in Korea

Background

Certain donor characteristics are known to be associated with increased graft failure in kidney transplantation.

Methods

We analyzed donor and recipient characteristics among deceased donor kidney transplantations performed from 1995 to 2008, excluding multiorgan, pediatric, and retransplantation cases.

Results

The 299 cases underwent analysis of donor characteristics including age, sex, cause of brain death, history of hypertension, cardiac arrest, length of intensive care unit (ICU) stay, last serum creatinine before organ donation, and change in creatinine during ICU stay. Cox regression analysis identified two factors that independently predicted a greater risk of graft failure. The factors were cerebrovascular accident (CVA) as the cause of brain death and a history of hypertension. Compared with donors with causes of brain death other than CVA, the adjusted hazard ratios for graft failure (GF) of kidneys from donors with CVA were 2.37 (1.34-4.19, P = .003). The hazard ratio for GF was 2.42 (1.34-4.37, P = .003) for kidneys from those with a history of hypertension. Donors meeting the criteria of CVA as the cause of brain death or history of hypertension comprised 43% of transplantation cases (128/299). Donor age and last serum creatinine level, which were identified in previous studies to show higher risks of graft failure, did not apply in our patients.

Conclusion

Donor history of hypertension and CVA as the cause of brain death were significant determinants of reduced graft survival after DDKT in Korea.     

Recurrence and Treatment Pattern in Long-Term Survivors with Hepatocellular Carcinoma: A Comparison between Radiofrequency Ablation and Surgery as a First-line Treatment

Background  

We compare the recurrence and treatment pattern in long-term survivors after radiofrequency ablation (RFA) and surgery for treatment of hepatocellular carcinoma (HCC).     

Effects of traditional “<Emphasis Type="Italic">Juci</Emphasis>” (contralateral acupuncture) on orofacial nociceptive behavior in the rat

Purpose “Juci”, one of the traditional acupuncture techniques, means contralateral acupuncture; i.e., implanting a needle into an acupoint to treat a given disease or disorder, but on the side of the body opposite to the diseased side. The aim of this study was: (1) to assess acupuncture effects on formalin-induced nociceptive behavior in the orofacial region in the rat, and (2) to evaluate the efficacy of Juci in the orofacial formalin test. Methods Forty-four adult male Wistar rats were used in the present study. A 1.0% formalin solution (25 μl s.c., diluted in saline) was injected into the right upper lip. The rats were randomly assigned to five groups. (1) The control group (n = 9), which received formalin injection without acupuncture pretreatment; (2) the ipsilateral Ho-ku (see note below) acupuncture group (n = 10); (3) the contralateral Ho-ku acupuncture group (n = 11); (4) the acupuncture plus naloxone group (n = 9), where intraperitoneal naloxone (1.0 mg·kg⁻¹) was injected immediately before acupuncture pretreatment; and (5) the sham acupuncture group (n = 5). “Ho-ku” is the term used for the “Large Intestine 4” acupoint, located between the first and second metacarpal bones. Results The injection of formalin produced the characteristic biphasic behavioral response. Acupuncture significantly inhibited the response in the early and late phases. Naloxone significantly reversed these effects. There were no statistically significant differences between the ipsilateral and Juci acupuncture groups. Sham acupuncture did not exert any significant effect on the formalin-induced behavior. Conclusion Our results showed that the degree of effectiveness of Juci was similar to that of the ipsilateral acupuncture technique. Therefore, the Juci technique is also useful for the treatment of orofacial pain.     

Real-time PCR assay compared with antigenemia assay for detecting cytomegalovirus infection in kidney transplant recipients

Human cytomegalovirus (CMV) infection is a major cause of morbidity and mortality among kidney transplant recipients. The CMVpp65 antigenemia assay has been used for preemptive therapy. Real-time polymerase chain reaction (PCR) technology for CMV DNA quantification in blood has demonstrated a good correlation with the currently employed CMV antigenemia assay. In this study, 90 renal transplant recipients were prospectively enrolled from July 2004 and May 2005. Monitoring of CMV infection was routinely performed with CMV antigenemia and real-time PCR assays. Real-time plasma PCR and CMV antigenemia assays were assessed on 797 samples. CMV antigenemia correlated with a positive CMV PCR (chi(2) = 78.05; P < .0001). Not only the positive rate but also the number of positive cells correlated with the number of PCR DNA copies (F = 26.07, r(2) = .25, P < .0001). To define an optimal cutoff value of CMV DNA load to initiate treatment in kidney transplant patients, we considered a CMV antigenemia titer of >50 positive cells per 400,000 leukocytes as the gold standard in our previous study. The optimal cutoff value for the quantitative real-time PCR assay was predicted to be 86 copies/microL. Thus, we observed that CMV real-time PCR assay would not completely replace antigenemia assay in kidney transplant recipients, but can be used complementarily to screen antigenemia and monitor preemptive therapy.