Acute acalculous cholecystitis following extended administration of nirmatrelvir/ritonavir for persistent SARS-CoV-2 infection.

Immunocompromised patients with hematologic malignancies, particularly those treated with anti-CD20 antibodies such as rituximab and obinutuzumab, are known to be at risk of prolonged infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Prolonged administration or combination therapy with antiviral medications reportedly yields favorable outcomes in these patients. However, knowledge regarding the adverse events associated with such therapeutic approaches is limited. Herein, we report a case of acute acalculous cholecystitis (AAC) following extended administration of nirmatrelvir/ritonavir (NMV/r) in a 68-year-old Japanese man with persistent SARS-CoV-2 infection. The patient had received obinutuzumab and bendamustine for follicular lymphoma and was diagnosed with coronavirus disease 2019 (COVID-19) approximately one year after treatment initiation with these drugs. Subsequently, he was admitted to a different hospital, where he received antiviral drugs, monoclonal antibodies, and steroids. Despite these interventions, the patient relapsed and was subsequently transferred to our hospital due to persistent SARS-CoV-2 infection. Remdesivir administration was ineffective, leading to the initiation of extended NMV/r therapy. One week later, he exhibited elevated gamma-glutamyl transpeptidase (GGT) levels, and one month later, he developed AAC. Cholecystitis was successfully resolved via percutaneous transhepatic gallbladder drainage and administration of antibiotics. We speculate that extended NMV/r administration, in addition to COVID-19, may have contributed to the elevated GGT and AAC. During treatment of persistent SARS-CoV-2 infection with extended NMV/r therapy, patients should be carefully monitored for the appearance of findings suggestive of biliary stasis and the development of AAC.

SIRIUS, Ultra-Scintillating Upconversion Breast Implant for Remote Orthotopic Photodynamic Therapy.

Present day strategies for delivery of wireless photodynamic therapy (PDT) to deep-seated targets are limited by the inadequacy of irradiance and insufficient therapeutic depth. Here we report the design and preclinical validation of a flexible wireless upconversion nanoparticle (UCNP) implant (SIRIUS) that is capable of large field, high intensity illumination for PDT of deep-seated tumors. The implant achieves this by incorporating submicrometer core-shell-shell NaYF4 UCNPs into its design, which significantly enhances upconversion efficiency and mitigates light loss from surface quenching. We demonstrate the efficacy of SIRIUS UCNP implant mediated PDT in preclinical breast cancer disease models. In our in vitro experiments, SIRIUS directed 5-Aminolevulinic Acid (5-ALA) based wireless PDT leads to significant reactive oxygen species (ROS) generation and tumor apoptosis in hormonal receptor+/HER2+ (MCF7) and triple-negative (MDA-MB-231) breast cancer cell lines. In our in vivo rodent model, SIRIUS-driven PDT is shown to be significant in regressing tumors when applied to orthotopically inoculated breast tumors. Following successful preclinical validation, we also describe a clinical prototype of UCNP breast implant with potential dual cosmetic and onco-therapeutic functions. SIRIUS is an upconversion breast implant for wireless PDT that fulfils all the design prerequisites necessary for seamless clinical translation.

Anterior cruciate ligament reconstruction with retained internal fixation hardware for treating Schatzker type V tibial plateau fracture: Two case reports.

Despite the high incidence of anterior cruciate ligament injury in patients with tibial plateau fractures, we found no reports about anterior cruciate ligament reconstruction with retained internal fixation hardware for these fractures. Herein, we report 2 male patients with Schatzker type V tibial plateau fractures and describe the use of retained hardware for internal fixation in tibia. The patients underwent anterior cruciate ligament reconstruction using outside-in technique for the femoral tunnel. Throughout the follow-up, no radiological symptoms of suspected knee osteoarthritis were observed. Accordingly, surgical intervention can be reduced by creating an independent femoral tunnel.

Chronic Kidney Disease Stage G4 in a Diabetic Patient Improved by Multi-Disciplinary Treatments Based Upon Literature Search for Therapeutic Evidence.

In the EMPA-REG OUTCOME trial, sodium-glucose cotransporter 2 (SGLT2) inhibitor, empagliflozin, reduced incident or worsening nephropathy. In the LEADER trial, a glucagon-like peptide 1 (GLP-1) receptor agonist, liraglutide, resulted in lower rates of the development and progression of diabetic kidney disease than placebo. Therefore, the American Diabetes Association and the European Association for the Study of Diabetes recommend the decision to treat high-risk individuals with a GLP-1 receptor agonist or SGLT2 inhibitor to reduce chronic kidney disease (CKD) progression should be considered. A 72-year-old male obese diabetic patient developed CKD stage G4 despite of use of both SGLT2 inhibitor and GLP-1 receptor agonist. We started using sodium bicarbonate because he showed metabolic acidosis due to uremia. We also started to use spherical carbonaceous adsorbent which adsorbs indole, the precursor of indoxyl sulfate, uremic toxin. We started the treatment with finerenone, a nonsteroidal, selective mineralocorticoid receptor antagonist, which has been recently shown to lower risks of CKD progression. Considering unfavorable effects of hyperuricemia on CKD, to treat his hyperuricemia, we started to use dotinurad, a novel selective urate reabsorption inhibitor, which reduces serum urate levels by selective inhibition of urate transporter 1. The improvement of CKD stage G4 in a diabetic patient was obtained by such multi-disciplinary treatments in addition to SGLT2 inhibitor and GLP-1 receptor agonist.

3D templating and patient-specific instrumentation in primary total knee arthroplasty with retained internal fixation hardware: Two case reports.

Two elderly female patients with Kellgren-Lawrence grade 4 knee osteoarthritis (KOA) having varus knee deformity and retained hardware for internal fixation in either femur or tibia underwent total knee arthroplasty (TKA) using 3D templating and patient-specific instrumentation (PSI). TKA was performed to treat KOA by minimally removing or without removing the retained hardware for the internal fixation of distal femoral or tibial diaphyseal fractures. Throughout a 2-year follow-up period, no superficial or deep infection was observed. In additions, no radiological symptoms of suspected component loosening were observed. Furthermore, both patients can currently walk without using crutches. 3D templating and PSI in primary TKA for patients with retained hardware for internal fixation of femoral or tibial fractures are considered suitable treatment options for reducing surgical invasion.

A case of insulinoma-induced hypoglycemia managed by Dexcom G4 Platinum.

This report details the case of a 41-year-old woman who was diagnosed with insulinoma. As the patient developed severe life-threatening hypoglycemia, we introduced Dexcom G4 Platinum (DG4P), a modern continuous glucose-monitoring system (CGM). The algorithm of the sensor glucose (SG) values of CGM is based on patients with diabThis report details the case of a 41-year-old woman who was diagnosed with insulinoma. As the patient developed severe life-threatening hypoglycemia, we introduced Dexcom G4 Platinum (DG4P), a modern continuous glucose-monitoring system (CGM). The algorithm of the sensor glucose (SG) values of CGM is based on patients with diabetes; therefore, we evaluated the accuracy of DG4P in this patient. The mean absolute relative differences and absolute differences between SG of DG4P and self-monitoring of blood sugar values were 10.8%±8.3% and 6.8±5.7 mg/dL, respectively, in the hypoglycemic region, which verifies DG4P's accuracy. DG4P was found to be useful for monitoring hypoglycemia not only in patients with diabetes but also in those with insulinoma.etes; therefore, we evaluated the accuracy of DG4P in this patient. The mean absolute relative differences and absolute differences between SG of DG4P and self-monitoring of blood sugar values were 10.8%±8.3% and 6.8±5.7 mg/dL, respectively, in the hypoglycemic region, which verifies DG4P's accuracy. DG4P was found to be useful for monitoring hypoglycemia not only in patients with diabetes but also in those with insulinoma.

Measurement of elastic strain recovery in an orthodontic aligner as a driving force for orthodontic treatment.

Orthodontic aligners undergo deformation during installation, producing an unexpected component of elastic restoring force that causes unintended changes in the dentition. The aim of this study was to investigate the relationship between strain and elastic recovery of the aligner. We distinguished the contributions to aligner deformation due to molding and installation by measuring the thickness distribution of an aligner after molding using micro-CT and tracking changes in grid patterns drawn on the sheet used to fabricate the aligner. The aligner was installed on a device that simulated canine movement. Although canine strain was quite strong around the cusp, and in premolar, it was observed mainly in their centers. Furthermore, after molding, thickness distribution of the aligner was found. But, it is no clear relationship between the thickness distribution and the strain distribution. Our method of analysis can help improve aligner design and establish molding method to deliver optimal orthodontic treatment.

The impact of relative hypotension on acute kidney injury progression after cardiac surgery: a multicenter retrospective cohort study.

BACKGROUND: Cardiac surgery is performed worldwide, and acute kidney injury (AKI) following cardiac surgery is a risk factor for mortality. However, the optimal blood pressure target to prevent AKI after cardiac surgery remains unclear. We aimed to investigate whether relative hypotension and other hemodynamic parameters after cardiac surgery are associated with subsequent AKI progression. METHODS: We retrospectively enrolled adult patients admitted to 14 intensive care units after elective cardiac surgery between January and December 2018. We defined mean perfusion pressure (MPP) as the difference between mean arterial pressure (MAP) and central venous pressure (CVP). The main exposure variables were time-weighted-average MPP-deficit (i.e., the percentage difference between preoperative and postoperative MPP) and time spent with MPP-deficit > 20% within the first 24 h. We defined other pressure-related hemodynamic parameters during the initial 24 h as exploratory exposure variables. The primary outcome was AKI progression, defined as one or more AKI stages using Kidney Disease: Improving Global Outcomes' creatinine and urine output criteria between 24 and 72 h. We used multivariable logistic regression analyses to assess the association between the exposure variables and AKI progression. RESULTS: Among the 746 patients enrolled, the median time-weighted-average MPP-deficit was 20% [interquartile range (IQR): 10-27%], and the median duration with MPP-deficit > 20% was 12 h (IQR: 3-20 h). One-hundred-and-twenty patients (16.1%) experienced AKI progression. In the multivariable analyses, time-weighted-average MPP-deficit or time spent with MPP-deficit > 20% was not associated with AKI progression [odds ratio (OR): 1.01, 95% confidence interval (95% CI): 0.99-1.03]. Likewise, time spent with MPP-deficit > 20% was not associated with AKI progression (OR: 1.01, 95% CI 0.99-1.04). Among exploratory exposure variables, time-weighted-average CVP, time-weighted-average MPP, and time spent with MPP < 60 mmHg were associated with AKI progression (OR: 1.12, 95% CI 1.05-1.20; OR: 0.97, 95% CI 0.94-0.99; OR: 1.03, 95% CI 1.00-1.06, respectively). CONCLUSIONS: Although higher CVP and lower MPP were associated with AKI progression, relative hypotension was not associated with AKI progression in patients after cardiac surgery. However, these findings were based on exploratory investigation, and further studies for validating them are required. Trial Registration UMIN-CTR, https://www.umin.ac.jp/ctr/index-j.htm , UMIN000037074.

Late-onset non-islet cell tumor hypoglycemia: A case report.

BACKGROUND: Hypoglycemia due to non-insulin-producing tumors is referred to as non-islet cell tumor hypoglycemia (NICTH). As NICTH is a rare lesion, the natural course of NICTH is not well understood. We report a case of NICTH that was observed 30 years before the onset of hypoglycemia. CASE SUMMARY: A 50-year-old man was diagnosed with an abnormal right chest shadow during a routine X-ray examination, but no further examination was undertaken because the lesion appeared benign. Thirty years after the tumor discovery, the patient was admitted to the hospital with symptoms of severe hypoglycemia, which was diagnosed as NICTH based on a complete examination. The tumor was resected and found to be a solitary fibrous mass (15.6 cm × 13.7 cm × 10.4 cm); thereafter, the patient's blood glucose levels normalized and he completely recovered. CONCLUSION: NICTH can have an acute onset, even if the tumor has been present and asymptomatic over a long time period.

Pain Deterioration Within 1 Year Predicts Future Decline of Walking Ability: A 7-Year Prospective Observational Study of Elderly Female Patients With Knee Osteoarthritis Living in a Rural District.

INTRODUCTION: Knee osteoarthritis (KOA) is commonly a main cause of locomotive syndrome. Consequently, appropriate timing of intervention is clinically important. MATERIALS AND METHOD: Fifty female patients of a primary care clinic in a rural district fulfilled the criteria for KOA and were recruited and underwent knee medical checkups. They initially underwent physical examination bilaterally of knees by an orthopedic surgeon, radiological evaluation, and they answered the outcome of Japanese Knee Osteoarthritis Measurement (JKOM). They were asked to answer JKOM 1 and 7 years after the initial checkup. Fourteen patients were lost to follow-up due to death or moving to a nursing home. Thirty-six patients were finally included and divided into 2 age-matched groups according to walking ability at the 7-year follow-up: group A, walking ability did not decline (n = 24), and group B, walking ability did decline (n = 12). The walking ability was measured as per ordinal classification as: 5 (walking without any aid), 4 (walking with a crutch), 3 (walking using walker), 2 (walking only possible in parallel bars), and 1 (wheelchair). We completed between-group comparisons of each of the 3 subsections of the JKOM (pain, limitation in mobility related to daily activity, and restriction of participation in social life and health perception), during each period. RESULTS: There were significant differences in JKOM pain score (12.9 vs 18.3, P = .0058) and total score (41.3 vs 55.8, P = .0093) between the groups at 1-year follow-up, even though base scores did not differ. DISCUSSION: Clinicians should pay attention to changes in perceived knee pain and should not continue prolonged conservative therapy in patients exhibiting rapid deterioration. CONCLUSION: Female patients with KOA whose pain deteriorated within 1 year may require early intervention to prevent future decline in walking ability.

Rotavirus gastroenteritis-associated urinary tract calculus in an infant.

Tsukida K, Goto M, Yamaguchi N, Imagawa T, Tamura D, Yamagata T. Rotavirus gastroenteritis-associated urinary tract calculus in an infant. Turk J Pediatr 2018; 60: 769-770. Rotavirus gastroenteritis a severe viral gastroenteritis that occasionally causes post-renal failure with urinary tract calculus. A 15-month-old boy with rotavirus gastroenteritis suffered from pre- and post-renal dysfunction due to dehydration and urinary obstruction, respectively. Careful evaluations using abdominal ultrasound and cautious fluid replacement with urine alkalization led to an improvement in the pre- and post-renal dysfunction.

A Case of Infrapatellar Fat Pad Ganglion of the Knee.

INTRODUCTION: A ganglion cyst can induce symptoms around the knee and should be considered as an intra-articular mass in differential diagnosis. CASE PRESENTATION: A 22-year-old female presented with a persistent medial knee joint pain in her left knee for 2 years. There was soft tissue swelling on the anteromedial aspect of the infrapatellar region on her left knee. Lachman and McMurray tests were negative. MRI showed a multilobular cyst in the infrapatellar fat pad with T1 low intensity and T2 STIR high intensity. The cyst was not attached to either meniscus. ACL and PCL looked normal.During surgery, the cyst was found to arise from the intra-patellar fat pad and was not attached to the menisci or synovium. The cyst was completely resected.Histological findings showed a multilobular cyst with a glassy fibrous tissue wall and clear jelly-like consistency, confirming the diagnosis of a ganglion. The patient recovered asymptomatically and has been without recurrence 7 years postoperatively. CONCLUSION: Differential diagnoses of an infrapatellar swelling are a meniscal cyst, synovial cyst, or ganglion. Most cases of cysts around the knee generate from fluid collection through meniscal tears. A ganglion cyst is a synovium-lined structure and is common around the wrist joint, but rare in the knee joint. A ganglion cyst in the knee joint often arises from ACL or PCL, but rarely arises from the infrapatellar fat pad. A ganglion cyst is one of the differential diagnoses of parameniscal cysts around the knee. We recommended an open resection with arthroscopic examination.

Liquid crystal holographic configurations for optically reconfigurable gate arrays.

An optically reconfigurable gate array (ORGA) system, which consists of an ORGA very large scale integration (VLSI), an easily rewritable liquid crystal holographic memory recording four configuration contexts, and a laser array, is proposed. Circuits on a gate array of the ORGA-VLSI can be programmed rapidly by exploiting large parallel connections between a holographic memory and a gate array VLSI; that programming can be executed even as it is being programmed. Consequently, the gate array can be switched from a certain circuit to another circuit instantaneously. We present a demonstration of the ORGA system and experimental results.

Multi-component behavior of fixed-bed adsorption of dioxins by activated carbon fiber.

The multi-component behavior of fixed-bed adsorption of dioxins (DXNs) was examined through detailed analyses of the concentration profiles of isomers in fixed-bed activated carbon fiber (ACF). Regularities in both adsorption rates and strengths were clarified. (1) The rate of transfer in the adsorption of polychlorinated dibenzo-p-dioxins and polychlorinated dibenzofurans (PCCDs/DFs) tends to increase with decreasing number of chlorine substituents. Axial dispersion also tends to increase with a decreasing number of chlorine substituents under our experimental conditions. (2) Homologues with the same number of chlorine substituents in PCDDs/DFs have similar adsorption strengths. The adsorption strength of PCDD/DF isomers is probably greater than that of co-planar polychlorinated biphenyls (co-PCB) isomers when the number of chlorine substituents is identical. (3) The adsorption strength of isomers depends on their molecular structure. In PCDDs/DFs the toxic isomers, all of which have vicinal chlorine substituents at the 2, 3, 7 and 8 positions, are relatively strong. It is clear, especially in TeCDDs, that isomers with vicinal chlorine substituents are stronger than isomers without. In co-PCBs, isomers without chlorine substituents at ortho positions are stronger than those with, and (4) A close analogy exists between the adsorption strength order for ACF and the elution order in gas chromatography (GC).

Screening of SLC25A13 mutations in early and late onset patients with citrin deficiency and in the Japanese population: Identification of two novel mutations and establishment of multiple DNA diagnosis methods for nine mutations.

We have recently identified SLC25A13 on chromosome 7q21.3 as the gene responsible for adult-onset type II citrullinemia (CTLN2) and found seven mutations in the SLC25A13 gene of CTLN2 patients. Most recently, the SLC25A13 mutations have been detected in neonatal/infantile patients with a type of neonatal hepatitis associated with cholestasis (NICCD). In the present study, we identified a novel mutation, E601X, in the SLC25A13 gene and established multiple DNA diagnosis methods for eight mutations by using a genetic analyzer with GeneScan and the single primer extension procedure (SNaPshot). An additional novel missense mutation (variation), E601K, was detected by SNaPshot analysis and was indistinguishable from the mutation E601X detected by the PCR/RFLP method. Multiple DNA diagnoses for the nine mutations revealed that 100 (male/female: 70/30) out of 115 CTLN2 and 38 (14/24) out of 45 NICCD patients tested were homozygotes or compound heterozygotes. The frequency of homozygotes carrying SLC25A13 mutations in both alleles is estimated to be minimally 1 in 21,000 from carrier detection (18 in 1,315 individuals tested) in the Japanese population. The differences in the gender ratio and in mutation types between CTLN2 and NICCD patients are significant. It is, however, unknown whether all homozygotes with mutated SLC25A13 in both alleles suffer from NICCD, CTLN2, both, or neither.

Pathogenesis and pathophysiology of citrin (a mitochondrial aspartate glutamate carrier) deficiency.

Adult-onset type II citrullinemia (CTLN2), characterized by a liver-specific deficiency of urea cycle enzyme, argininosuccinate synthetase, is caused by mutations in SLC25A13 that encodes a calcium binding mitochondrial solute carrier protein, citrin. Citrin deficiency causes not only CTLN2 but also neonatal intrahepatic cholestasis caused by citrin deficiency at neonatal period. Moreover citrin and its isoform aralar were found to be aspartate glutamate carrier. From the viewpoint of the metabolic functions of citrin as aspartate glutamate carrier in urea synthesis and NADH shuttle, symptoms of CTLN2 and neonatal intrahepatic cholestasis caused by citrin deficiency are analyzed.