Delayed exacerbation of COVID-19 pneumonia in vaccinated kidney transplant recipients receiving immunosuppressants: a case series.

Coronavirus disease 2019 (COVID-19) increases the risk of mortality and hospitalization in immunocompromised patients, including kidney transplant recipients (KTRs) receiving immunosuppressants. Several vaccines for COVID-19 have been developed and proven effective in decreasing the incidence of COVID-19 and the rate of progression to severe COVID-19. However, breakthrough infections have also been reported in vaccinated patients. We report cases from our center of delayed exacerbated pneumonia from COVID-19 in vaccinated KTRs receiving immunosuppressants. Of the 900 KTRs who had been vaccinated for COVID-19 and were followed up at our center from January 1, 2022, to April 30, 2022 (during the Omicron variant outbreak), 126 contracted COVID-19 (incidence rate, 14%). Thirty-four (27%) in this group were hospitalized due to COVID-19. Twenty patients did not have pneumonia but had symptoms of upper respiratory tract infection or diarrhea, which improved with conservative treatment. Nine of the 14 patients with pneumonia had delayed onset or exacerbated pneumonia 1 week after their COVID-19 diagnosis. They were treated with remdesivir, and most recovered. One patient died due to progressive pneumonia and pneumothorax. It is important that KTRs who are taking immunosuppressants be observed closely and for a prolonged period after a COVID-19 diagnosis, irrespective of their COVID-19 vaccination status.

Development and Characterization of Low Temperature Wafer-Level Vacuum Packaging Using Cu-Sn Bonding and Nanomultilayer Getter.

Most microsensors are composed of devices and covers. Due to the complicated structure of the cover and various other requirements, it difficult to use wafer-level packaging with such microsensors. In particular, for monolithic microsensors combined with read-out ICs, the available process margins are further reduced due to the thermal and mechanical effects applied to IC wafers during the packaging process. This research proposes a low-temperature, wafer-level vacuum packaging technology based on Cu-Sn bonding and nano-multilayer getter materials for use with microbolometers. In Cu-Sn bonding, the Cu/Cu3Sn/Cu microstructure required to ensure reliability can be obtained by optimizing the bonding temperature, pressure, and time. The Zr-Ti-Ru based nanomultilayer getter coating inside the cap wafer with high step height has been improved by self-aligned shadow masking. The device pad, composed of bonded wafer, was opened by wafer grinding, and the thermoelectrical properties were evaluated at the wafer-level. The bonding strength and vacuum level were characterized by a shear test and thermoelectrical test using microbolometer test pixels. The vacuum level of the packaged samples showed very narrow distribution near 50 mTorr. This wafer-level packaging platform could be very useful for sensor development whereby high reliability and excellent mechanical/optical performance are both required. Due to its reliability and the low material cost and bonding temperature, this wafer-based packaging approach is suitable for commercial applications.

Investigation of Integrated Reactive Multilayer Systems for Bonding in Microsystem Technology.

For the integration of a reactive multilayer system (iRMS) with a high exothermic reaction enthalpy as a heat source on silicon wafers for low-temperature bonding in the 3D integration and packaging of microsystems, two main conflicting issues should be overcome: heat accumulation arising from the layer interface pre-intermixing, which causes spontaneous self-ignition during the deposition of the system layers, and conductive heat loss through the substrate, which leads to reaction propagation quenching. In this work, using electron beam evaporation, we investigated the growth of a high exothermic metallic Pd/Al reactive multilayer system (RMS) on different Si-wafer substrates with different thermal conduction, specifically a bare Si-wafer, a RuOx or PdOx layer buffering Si-wafer, and a SiO2-coated Si-wafer. With the exception of the bare silicon wafer, the RMS grown on all other coated wafers underwent systematic spontaneous self-ignition surging during the deposition process once it reached a thickness of around 1 µm. This issue was surmounted by investigating a solution based on tuning the output energy by stacking alternating sections of metallic reactive multilayer Pd/Al and Ni/Al systems that have a high and medium enthalpy of exothermic reactions, respectively. This heterostructure with a bilayer thickness of 100 nm was successfully grown on a SiO2-coated Si-wafer to a total thickness of 3 µm without any spontaneous upsurge of self-ignition; it could be electrically ignited at room temperature, enabling a self-sustained propagating exothermic reaction along the reactive patterned track without undergoing quenching. The results of this study will promote the growth of reactive multilayer systems by electron beam evaporation processing and their potential integration as local heat sources on Si-wafer substrates for bonding applications in microelectronics and microsystems technology.

Allograft dysfunction and parenchymal necrosis associated with renal artery stenosis and perigraft hematoma after kidney transplantation.

Transplant renal artery stenosis (TRAS) is one cause of allograft dysfunction. TRAS causes parenchymal necrosis and graft insufficiency. Herein, we report the case of a 40-year-old female with end-stage renal disease due to immunoglobulin A nephropathy, who underwent kidney transplantation with her elder sister. The surgery was successful and the allograft showed primary graft function. At postoperative day (POD) 2, urine output decreased sharply. We checked a non-enhanced abdominal computed tomography scan which showed subcapsular and pelvic cavity hematomas. She underwent hematoma removal surgery with renal upper polar capsulotomy. Bleeding control was successful, but her serum creatinine was 5.4 mg/dL. At POD 25, abdomen magnetic resonance angiography showed significant stenosis at the anastomosis site between the graft renal artery and the recipient's internal iliac artery. Then, percutaneous transluminal angioplasty was implemented. Significant stenosis (>80%) was detected at the anastomotic site and a 5-mm stent was inserted at stenotic lesion with post-stent balloon angioplasty using a 5-mm balloon catheter. The renal arterial diameter and blood flow were normalized. At postoperative 5 months, a 99mTc dimercaptosuccinic acid scan showed multiple focal radioisotope defects. At 54 months after renal transplantation, her serum creatinine level was 4.0 mg/dL and her glomerular filtration rate was 13 mL/min/1.73 m2. Hence, we report that TRAS can cause parenchymal necrosis and allograft dysfunction.

Long-term Survival Analysis of Kidney Transplant Recipients Receiving Mizoribine as a Maintenance Immunosuppressant: A Single-Center Study.

BACKGROUND: Mizoribine (MZR) has been developed as an immunosuppressant and is widely used in Asia. However, most studies on MZR have been performed in Japan, and there remains a lack of reports on long-term use in other countries. The purpose of this study is to evaluate the efficacy and safety of MZR's use in Korean kidney transplant recipients by observing their clinical courses and analyzing their long-term patent and graft survival rates. METHODS: We studied 129 subjects who had received MZR as a maintenance immunosuppressant since January 2000. Our analysis was based on the patients' medical records from January 2000 to December 2017. RESULTS: The overall survival rates of the kidney transplant recipients were 100% at 1 year, 99.1% at 5 years, 96.8% at 10 years, and 92.5% at 15 years. The graft survival rates were 100% at 1 year, 98.3% at 5 years, 93.2% at 10 years, and 82.2% at 15 years. There were differences in the recipient survival and graft survival rates according to the kidney donor and the use of renal replace therapy before transplant. There were no differences in the survival rates according to the MZR dose, the type of underlying disease, or other clinical factors. CONCLUSIONS: The use of low doses of MZR as a maintenance immunosuppressant could be an effective means of ensuring relatively good long-term patient and graft survival rates in cases of kidney transplant.

Efficacy and Safety of Ultra-Low-Dose Valganciclovir Chemoprophylaxis for Cytomegalovirus Infection in High-Risk Kidney Transplantation Patients.

INTRODUCTION: Valganciclovir (VGCV) prophylaxis of 900 mg twice daily for 6 months is recommended to prevent cytomegalovirus (CMV) infection, which is a major cause of decreased graft and patient survival in kidney transplant recipients. However, recent studies have shown the efficacy of 900 mg once daily for 3 to 6 months. Maintaining VGCV compliance is difficult because of high drug costs and side effects, such as thrombocytopenia and leukopenia. Therefore, we studied the efficacy of ultra-low dose, short-duration VGCV (450 mg every other day for 3 months) in preventing CMV infection in ABO-incompatible (ABOiKT) and deceased donor kidney transplant (DDKT) recipients. METHODS: We retrospectively reviewed the medical records of all kidney transplant patients > 18 years old treated at Bong Seng Memorial Hospital from June 2009 to July 2016 who received ultra-low-dose VGCV prophylaxis (450 mg every other day for 3 months). The review included 74 CMV seropositive donor/seropositive recipient (D+/R+) ABOiKT and 78 CMV D+/R+DDKT recipients. The primary outcome was occurrence of CMV infection. Secondary outcomes were graft and patient survival and hematologic side effects. RESULTS: Mean prophylaxis and follow-up were 3 and 98 months, respectively. CMV disease occurrence was significantly higher in DDKT than in ABOiKT (12 cases, 8.1%, vs 1 case, .7%, P < .01). There were no significant differences in patient survival rate, graft survival rate, or hematologic side effects between the groups. CONCLUSION: Ultra-low-dose VGCV prophylaxis to prevent CMV infection is effective in ABOiKT, but other treatment protocols are needed for DDKT patients.

Development and Characterization of Non-Evaporable Getter Thin Films with Ru Seeding Layer for MEMS Applications.

Mastering non-evaporable getter (NEG) thin films by elucidating their activation mechanisms and predicting their sorption performances will contribute to facilitating their integration into micro-electro-mechanical systems (MEMS). For this aim, thin film based getters structured in single and multi-metallic layered configurations deposited on silicon substrates such as Ti/Si, Ti/Ru/Si, and Zr/Ti/Ru/Si were investigated. Multilayered NEGs with an inserted Ru seed sub-layer exhibited a lower temperature in priming the activation process and a higher sorption performance compared to the unseeded single Ti/Si NEG. To reveal the gettering processes and mechanisms in the investigated getter structures, thermal activation effect on the getter surface chemical state change was analyzed with in-situ temperature XPS measurements, getter sorption behavior was measured by static pressure method, and getter dynamic sorption performance characteristics was measured by standard conductance (ASTM F798⁻97) method. The correlation between these measurements allowed elucidating residual gas trapping mechanism and prediction of sorption efficiency based on the getter surface poisoning. The gettering properties were found to be directly dependent on the different changes of the getter surface chemical state generated by the activation process. Thus, it was demonstrated that the improved sorption properties, obtained with Ru sub-layer based multi-layered NEGs, were related to a gettering process mechanism controlled simultaneously by gas adsorption and diffusion effects, contrarily to the single layer Ti/Si NEG structure in which the gettering behavior was controlled sequentially by surface gas adsorption until reaching saturation followed then by bulk diffusion controlled gas sorption process.