The advent of immune checkpoint inhibitors (ICIs) has significantly improved the prognosis of patients with advanced malignancies. On the other hand, these drugs might cause immune-related adverse ...events (irAEs) including endocrinopathies and nephropathies. Thyroid dysfunction is one of the most common irAEs. For ICIs-induced nephropathies, most cases are due to tubulointerstitial nephritis, which might require steroid treatment. Here, we report a patient with non-small cell lung cancer treated with ICI who developed increased serum creatinine (s-Cr) levels due to ICIs-induced hypothyroidism.
A 57-year-old Asian man with refractory non-small cell lung cancer under ICIs therapy (pembrolizumab, an anti-programmed cell death-1 monoclonal antibody) developed increased s-Cr levels 5 months after the pembrolizumab initiation. His laboratory data, renal biopsy, and Gallium-67 scintigraphy findings denied pembrolizumab-induced tubulointerstitial nephritis. His renal function was correlated with thyroid function. Despite the increase of s-Cr levels, serum cystatin C levels were normal, which could be explained by the hypothyroidism. Levothyroxine treatment improved renal function as well as thyroid function. Then pembrolizumab was resumed, and both his thyroid and renal function remained normal level. Ultimately, we concluded that the increased s-Cr levels were caused by pembrolizumab-induced hypothyroidism.
All clinicians involved in ICI treatment need to recognize the possible increase in s-Cr levels caused by ICIs-induced hypothyroidism, and we propose monitoring serum cystatin C levels to differentiate ICIs-induced hypothyroidism from tubulointerstitial nephritis before invasive renal biopsies or steroid treatment, which are recommended by the prescribing information for pembrolizumab, are performed.
Background:The aim of the eccentric rotational acetabular osteotomy is to correct the deficient acetabular coverage in the dysplastic hip in order to limit the development of secondary ...osteoarthritis. The purpose of this study was to investigate the results in patients managed with an eccentric rotational acetabular osteotomy after a mean of twenty years.Methods:The clinical and radiographic outcomes for the first 126 consecutive patients (132 hips) who underwent an eccentric rotational acetabular osteotomy at our institution were retrospectively evaluated. One hundred and twenty-four patients (130 hips) were evaluated; 117 were women (123 hips). The mean patient age was thirty-seven years (range, fifteen to fifty-nine years) at the time of surgery, and the average duration of follow-up was twenty years. Twenty-three hips in twenty-two patients were also treated with intertrochanteric valgus osteotomy at the time of the eccentric rotational acetabular osteotomy to further improve joint congruency.Results:The mean preoperative Harris hip score of 70 points (range, 51 to 90 points) improved to a mean of 88 points (range, 35 to 100 points) at the final follow-up. Thirty hips had a fair clinical outcome (Harris hip score, <80 points). In seventeen hips, the eccentric rotational acetabular osteotomy was converted to a total hip arthroplasty. The cumulative survivorship at fifteen years and at the final follow-up at twenty-three years was 97% and 80%, respectively. Four factors led to a poor outcome: a small ( less than or equal to 2.0-mm) preoperative minimum joint space, joint incongruence, simultaneous intertrochanteric valgus osteotomy, and lateral subluxation of the femoral head postoperatively.Conclusions:Eccentric rotational acetabular osteotomy is an effective surgical procedure for treating symptomatic dysplastic hips before, and in the early stages of, osteoarthritis. The majority of patients maintained excellent or good native hip function at a mean of twenty years after surgery.Level of Evidence:Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Background and aim
Various techniques for direct biopsy from gastrointestinal subepithelial tumors (SETs) have been reported, although no standard method has been established. A common feature of ...these techniques is the removal of overlaying mucosa to enable direct biopsies from the SETs. These methods have been synthesized under the collective term “unroofing technique”. We conducted a multicenter retrospective study to assess its efficacy and identify potential complications.
Methods
This study was conducted in 10 hospitals and involved all eligible patients who underwent unroofing techniques to obtain biopsies for gastrointestinal SETs between April 2015 and March 2021. The primary endpoint was the diagnostic accuracy of the unroofing technique, and the secondary endpoints were the incidence of adverse events and the factors contributing to the accurate diagnosis.
Results
The study included 61 patients with 61 gastrointestinal SETs. The median tumor size was 20 mm, and the median procedure time was 38 min, with 82% successful tumor exposure. The rate of pathological diagnosis was 72.1%. In 44 patients with a pathological diagnosis, two showed discrepancies with the postresection pathological diagnosis. No factors, including facility experience, organ, tumor size, or tumor exposure, significantly affected the diagnostic accuracy. There was one case of delayed bleeding and two cases of perforation.
Conclusion
The diagnostic yield of the unroofing technique was acceptable. The unroofing technique was beneficial regardless of institutional experience, organ, tumor size, or actual tumor exposure.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Background
Environmental factors are suggested to affect the pathogenesis of several diseases, including inflammatory bowel disease (IBD). The seasonality of disease onset and exacerbation in IBD, ...however, are not well established. We herein aimed to clarify the disease seasonality and to investigate the underlying characteristics in IBD patients exhibiting seasonality of the disease course.
Methods
This was a multicenter observational study comprising 20 institutions (Osaka Gut Forum) in Japan. Data were collected from November 2013 to August 2014 using survey forms for physicians and questionnaires for patients. Multivariate analysis was performed to clarify the independent factors affecting disease seasonality.
Results
A total of 1055 patients, including 298 patients with Crohn’s disease (CD) and 757 patients with ulcerative colitis (UC), were enrolled. The proportion of CD patients with disease onset in the summer was significantly larger than that in the other seasons, while UC patients exhibited no seasonality of disease onset. More than half of the IBD patients (51.1%) experienced seasonal exacerbation of IBD, and winter was the most common season for disease exacerbation in both CD and UC patients. Seasonality of disease onset and exacerbation was observed in young-onset patients (≤40 years old), but not in elderly-onset patients. Age at onset was independently associated with the seasonality of both disease onset and exacerbation.
Conclusions
Seasonality of disease onset and exacerbation was observed especially in young-onset IBD patients. Underlying pathophysiologic triggers for disease initiation and exacerbation may be influenced by age at disease onset.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Assessment of kidney biopsies provides crucial information for diagnosis and disease activity, as well as prognostic value. Kidney biopsy specimens occasionally contain veno-muscular complex (VMC), ...which consists of muscle tissues around the kidney venous system in the corticomedullary region. However, the role of VMC and the clinical significance of VMC variants is poorly understood. In the present study, we investigated VMC variants’ kidney prognostic values.
Retrospective cohort study.
Among 808 patients who underwent a kidney biopsy from 2011 to 2019, 246 patients whose kidney biopsy specimens contained VMC were enrolled.
VMC variants; Inflammatory-VMC (an infiltration of ≥80 inflammatory cells/mm2-VMC area) and VMC hypertrophy (Hyper-VMC, a VMC average width ≥850 μm), and the interstitial fibrosis/tubular atrophy (IFTA) score.
A decline in eGFR ≥40% from the baseline or commencement of kidney replacement therapy.
Cox proportional hazards model.
Among 246 patients with data on VMC, mean baseline eGFR was 56.0±25.6 ml/min per 1.73 m2; 80 had high inflammatory VMC and 62 had VMC hypertrophy. There were 51 kidney events over median follow-up of 2.5 years. We analyzed two VMC variants: Multivariable logistic regression analysis revealed that eGFR negatively correlated with the presence of both Inflammatory-VMC and Hyper-VMC. A Cox proportional hazards analysis revealed that Inflammatory-VMC (but not Hyper-VMC) was independently associated with the primary outcome after adjustments for known risk factors of progression, including proteinuria, eGFR and the interstitial fibrosis/tubular atrophy (IFTA) score (hazard ratio (HR) 1.97; 95% confidence interval, 1.00 to 3.91).
Single-center study and small sample size.
Assessment of Inflammatory-VMC provides additional kidney prognostic information to known indicators of kidney disease progression in patients who undergo kidney biopsy.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
Background and study aims
Although new image-enhanced endoscopy (IEE) technologies such as blue laser imaging (BLI), BLI-bright, and linked color imaging (LCI) have been developed, their ...utility for the detection of sessile serrated adenoma/polyps (SSA/Ps) is still unclear. This study aimed to evaluate the utility of BLI, BLI-bright, and LCI for SSA/P detection in still image examinations and in a prospective randomized controlled trial (RCT).
Patients and methods
A group of 6 expert and non-expert endoscopists read 200 endoscopic still images containing SSA/P lesions using white light image (WLI), BLI, BLI-bright, and LCI. Color differences were calculated using the color space method. A prospective RCT of tandem colonoscopy with WLI and LCI was performed. Patients with SSA/P and those with a history of SSA/P that had been endoscopically removed were enrolled and randomly allocated to WLI-LCI or LCI-WLI groups. Additional endoscopic detection rates for SSA/P were compared between the 2 groups.
Results
LCI showed the highest SSA/P detection rate among the 4 modes for both expert and non-expert endoscopists. The detection rate with LCI for the 6 expert endoscopists (mean 98.3 ± standard deviation 2.0 %) was significantly higher than that with WLI (86.7 ± 6.0 %,
P
< 0.01). Likewise, the detection rate with LCI for the 6 non-expert endoscopists (92.3 ± 2.9 %) was significantly higher than that with WLI (72.7 ± 11.5 %,
P
< 0.01). The color difference of SSA/P with LCI was the highest among the 4 modes, and was significantly higher than with WLI (median 15.9, (interquartile range 13.7 – 20.6) vs. 10.2, (7.6 – 14.2);
P
< 0.0001). In the RCT, a total of 44 patients (WLI-LCI 22 vs. LCI-WLI 22) underwent colonoscopy. The additional detection rate for SSA/P in the second inspection in the WLI-LCI group (21.6 %, 8/37) was significantly higher than in the LCI-WLI group (3.2 %, 1/31;
P
= 0.02). The small, flat, non-mucus and isochromatic SSA/Ps in the transverse colon were detected more frequently in the second inspection with LCI.
Conclusions
LCI was the most sensitive mode for SSA/P detection among WLI, BLI, BLI-bright, and LCI in the still image examinations. Our RCT strongly suggests that LCI is superior to conventional WLI for SSA/P detection during colonoscopy. UMIN000017599.
Paraneoplastic syndromes are generally defined as clinical disorders associated with malignant diseases, and hypocalcemia associated with cancer is a rare condition. A woman in her 60s was referred ...to our hospital for the further examination of massive ascites due to carcinoma of unknown primary origin. She complained of numbness around her lips, and marked hypocalcemia of 5.0 mg/dL was noted. After two courses of chemotherapy, computed tomography showed a decrease in the ascites, and her serum calcium level increased. Although hypocalcemia is a very rare condition in patients with gastric cancer, serum calcium values should be evaluated when neurological symptoms are observed.
Periprosthetic osteolysis is a serious problem that limits long-term survival of total hip arthroplasty. Ceramics have been introduced as a joint surface material to reduce osteolysis due to wear ...particles. The aim of this study is to investigate the biological reaction of ceramic particles on murine calvarial bone, in comparison with polyethylene and titanium particles. Sixty CL/BL6 mice were divided into five groups according to the materials implanted onto the murine calvariae: control, Al
2O
3, ZrO
2, high-density polyethylene (HDP) and Ti6Al4V. One week after the implantation, each calvarial tissue was dissected and the release of proinflammatory mediators (IL-1
β, IL-6, TNF-
α) and bone resorption were assessed. The particles of HDP and Ti6Al4V induced three and two times larger osteolytic lesions than the control, respectively. The levels of IL-1
β and IL-6 were significantly elevated in the medium subcultured with the calvariae of HDP and Ti6Al4V groups. Any particle type did not increase the levels of TNF-
α. There were no significant differences observed in the levels of proinflammatory mediators or osteolytic area among Al
2O
3, ZrO
2 and control groups. The inflammatory response and bone resorption induced by ceramic particles were much smaller than those induced by HDP and Ti6Al4V. These biological features suggest the biocompatibility of ceramics as a joint surface material for artificial joints.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
While hypothyroidism increases serum creatinine (Cr) levels, it is uncertain whether the elevation is mediated via a decline in the glomerular filtration rate (GFR) or the reflection of enhanced Cr ...production from the muscles or both. In the present study, we explored an association between urinary Cr excretion rate (CER) and hypothyroidism. A total of 553 patients with chronic kidney disease were enrolled in a cross-sectional study. Multiple linear regression analysis was performed to explore the association between hypothyroidism and urinary CER. The mean urinary CER was 1.01 ± 0.38 g/day and 121 patients (22%) had hypothyroidism. The multiple linear regression analysis revealed explanatory variables with urinary CER, including age, sex, body mass index, 24 h Cr clearance (24hrCcr), and albumin while hypothyroidism was not considered an independent explanatory variable. In addition, scatter plot analysis with regression fit line representing the association between estimated GFR calculated using s-Cr (eGFRcre) and 24hrCcr revealed that eGFRcre and 24hrCcr had strong correlations with each other in hypothyroid patients as well as euthyroid patients. Collectively, hypothyroidism was not considered an independent explanatory variable for urinary CER in the present study and eGFRcre is a useful marker to evaluate kidney function regardless of the presence of hypothyroidism.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Nonalcoholic fatty liver disease (NAFLD) is known to be strongly associated with obesity, visceral fat, metabolic syndrome (MS), lifestyle, and lifestyle-related diseases in both males and females. ...However, the prevalence of NAFLD, MS, and clinical backgrounds is different between males and females.
We conducted a cross-sectional study to examine the differing influence of lifestyle-related factors and visceral fat on fatty liver (FL) with elevation of liver enzymes between males and females with MS.
We enrolled 42,134 persons who underwent a regular health check-up, and after excluding subjects who fulfilled excluding criteria, the remaining subjects were 2,110 persons with MS. We examined the differing influence of lifestyle-related factors and visceral fat on FL with elevation of alanine aminotransferase (ALT) (ALT elevation was defined as ALT level of ≥31 IU/l in the present study).
The odds rations for FL with ALT elevation were as follows: WC, 1.83 (95% confidence interval (CI) 1.36-2.46); dyslipidemia, 1.89 (95% CI 1.34-2.68); hemoglobin A1c, 1.36 (95% CI 1.00-1.85); visceral fat type MS (V-type MS), 5.78 (95% CI 4.29-7.80); and light drinker, 0.56 (95% CI 0.41-0.78) in males with MS and BMI, 2.18 (95% CI 1.43-3.33); WC, 1.85 (95% CI 1.27-2.70); diastolic blood pressure, 1.69 (95% CI 1.16-2.45); triglyceride, 2.22 (95% CI 1.56-3.17); impaired glucose tolerance, 1.66 (95% CI 1.11-2.47); and V-type MS, 3.83 (95% CI 2.57-5.70) in females with MS. The prevalence of FL with ALT elevation and ALT was significantly higher in V-type MS than in the subcutaneous fat type MS in both males and females with MS (P < 0.001).
Although V-type MS and WC is a common significant predictor of an increased prevalence of FL with ALT elevation in both males and females with MS, gender, lifestyle-related factors, and MS type in individuals with MS should be considered for the development of FL with ALT elevation.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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