A Case of Thrombocytopenia, Anasarca (Edema, Pleural Effusion, and Ascites), Fever, Reticulin Fibrosis/Renal Dysfunction, and Organomegaly (TAFRO) Syndrome Initially Not Presenting With Thrombocytopenia: A Role of Immature Platelet Fraction.

Thrombocytopenia, anasarca (edema, pleural effusion, and ascites), fever, reticulin fibrosis/renal dysfunction, and organomegaly (TAFRO) syndrome is a rare and severe systemic disease. The emergence of thrombocytopenia, however, may be preceded by other signs or symptoms, which could delay the diagnosis of the disease. We reported a case in which an increased immature platelet fraction (IPF), a surrogate marker for megakaryocytic activity, preceded the development of thrombocytopenia, and finally, we diagnosed the patient with TAFRO syndrome. A 79-year-old male with a previous history of uninephrectomy due to bladder and ureteral cancer was admitted to our hospital because of massive edema and progressive impairment in renal function. On admission, inguinal lymphadenopathy, elevated C-reactive protein (CRP), bilateral pleural effusion, and ascites were observed, and the lymph node biopsy showed that atrophic lymphoid follicles and germinal centers were observed along with prominent glomeruloid vascular proliferation and the expansion of the interfollicular spaces consistent with the feature of Castleman's disease. The peripheral platelet count did not reach the level of the criteria for TAFRO syndrome (13.9×104/µL), but the immature platelet fraction was increased (11.6%), and bone marrow biopsy revealed hyperplasia of megakaryocytes. During the course of the preemptive treatment with prednisolone and tocilizumab, thrombocytopenia was uncovered, and the patient was finally diagnosed as having TAFRO syndrome. Thus, the present case may offer valuable information on the role of the immature platelet fraction in the establishment of the early diagnosis of TAFRO syndrome.

Validation study of EuroSCORE II for dialysis patients: A single-center study in Japan.

BACKGROUND: The European System for Cardiac Operative Risk Evaluation (EuroSCORE) II is a predictive model for in-hospital mortality after cardiac surgery. Although it has good performance among the general population undergoing cardiac surgery, it has not been validated among dialysis patients, who have a higher rate of mortality after cardiac surgery. This study aimed to evaluate the performance of the model in predicting in-hospital mortality in maintenance dialysis patients undergoing cardiac surgery. METHODS: This retrospective, single-center study included adult patients on maintenance dialysis who underwent open cardiac surgery at our institution. Calibration performance of EuroSCORE II for in-hospital death was determined based on the comparison between expected and observed mortalities for low- (EuroSCORE II <4 %), intermediate- (4-8 %), and high-risk (>8 %) groups. The area under receiver operating characteristic curve (AUROC) was investigated to determine the model's discrimination performance. RESULTS: A total of 163 patients (male, 73.6 %; median age, 70 years; median dialysis vintage, 9 years; median EuroSCORE II, 3.3 %) were included. The mortality rate was 9.2 %. The observed mortality rates (vs. mean expected mortality) rates were 2.1 % (vs. 2.4 %), 7.5 % (vs. 5.5 %), and 34.5 % (vs. 21.1 %) in the low-, intermediate-, and high-risk groups, respectively. Its AUROC was 0.825 (95 % confidence interval, 0.711-0.940). CONCLUSIONS: Although EuroSCORE II model adequately estimated in-hospital mortality in the low-and intermediate-risk groups (EuroSCORE II <8 %), it underestimated in-hospital mortality in the high-risk group (EuroSCORE II >8 %) among maintenance dialysis patients. The discrimination performance of the model for in-hospital death was good among maintenance dialysis patients.

Crowned dens syndrome: A case series of 72 patients at eight teaching hospitals in Japan.

Background: Crowned dens syndrome (CDS) is characterized by calcification around the odontoid process, accompanied by neck pain. Although CDS is supposedly rare, we regularly diagnose and manage this condition, indicating a perception gap between previous studies and our experience. The purpose of this study was to determine the annual incidence of CDS, time to diagnosis in CDS, as well as the features of CDS. Methods: The study design was a retrospective case series study conducted at eight teaching hospitals in Japan. We identified CDS cases from April 2013-March 2015. CDS was diagnosed when patients had acute onset of neck pain and CT showed calcification around the dens and when other diagnoses were unlikely. Results: Seventy-two CDS cases were identified. Mean annual incidence was 4.6 ± 2.3 cases at each hospital. Among those with available data, 57 of 64 had limited rotation (89.1%). The diagnosis of CDS was made in general internal medicine or the emergency medicine department in 61 cases (84.7%). A total of 62 cases (86.1%) were diagnosed within 1 day of presentation, and the median time from initial presentation at the hospital to diagnosis was 0.0 days (25th-75th percentiles, 0.0-1.0). For treatment, NSAIDs were used in 56cases (77.8%) and acetaminophen in 20 cases (27.8%). Conclusion: CDS might be more common than has been reported to date. Time to diagnosis of CDS was within 1 day of visiting a teaching hospital. Cervical motion restriction is common in CDS and may be useful in establishing the diagnosis.

Sustained effect of leukocytapheresis/granulocytapheresis versus anti-human TNF-α monoclonal antibody on ulcerative colitis: A 2-year retrospective study.

Although anti-tumor necrosis factor-α monoclonal antibody biological preparations (BP) agents are widely used as an established treatment tool for refractory ulcerative colitis (UC), whether leukocytapheresis/granulocytapheresis (L/G-CAP) has similar beneficial impact on the disease activity remains undetermined. Furthermore, the costs defrayed for the treatment with these 2 modalities have not been compared. We retrospectively evaluated whether L/G-CAP offered sustained beneficial effects over 2-year period. The patients who had moderately to severely active UC (Rachmilewitz clinical activity index (CAI) ≧ 5) and were treated with a series (10 sessions) of L/G-CAP (n = 19) or BP (n = 7) as an add-on therapy to conventional medications were followed. Furthermore, the cost-effectiveness pertaining to the treatment with L/G-CAP and BP was assessed over 12 months. At baseline, L/G-CAP and BP groups manifested similar disease activity (CAI, L/G-CAP; 7.0 [6.0-10.0], BP; 10.0 [6.0-10.0], P = .207). The L/G-CAP and BP treatment suppressed the activity, with CAI 1 or less attained on day 180. When the L/G-CAP group was dichotomized into L/G-CAP-high and L/G-CAP-low group based on CAI values (≥3 or < 3) on day 365, CAI was gradually elevated in L/G-CAP-high group but remained suppressed in L/G-CAP-low group without additional apheresis for 2 years. Anemia was corrected more rapidly and hemoglobin levels were higher in BP group. The cost of the treatment with L/G-CAP over 12 months was curtailed to 76% of that with BP (1.79 [1.73-1.92] vs 2.35 [2.29-3.19] million yen, P = .028). L/G-CAP is as effective as BP in a substantial number of patients over 2 years. The cost for the treatment of UC favors L/G-CAP although the correction of anemia may prefer BP. Thus, L/G-CAP can effectively manage the disease activity with no additional implementation for 2 years although further therapeutic modalities might be required in a certain population with high CAI observed on day 365.

Impact of early initiation of renin-angiotensin blockade on renal function and clinical outcomes in patients with hypertensive emergency: a retrospective cohort study.

BACKGROUND: Hypertensive emergency is a critical disease that causes multifaceted sequelae, including end-stage kidney disease and cardiovascular disease. Although the renin-angiotensin-aldosterone (RAA) system is enormously activated in this disease, there are few reports that attempt to characterize the effect of early use of RAA inhibitors (RASi) on the temporal course of kidney function. METHODS: This retrospective cohort study was conducted to clarify whether the early use of RASi during hospitalization offered more favorable benefits on short-term renal function and long-term renal outcomes in patients with hypertensive emergencies. We enrolled a total of 49 patients who visited our medical center with acute severe hypertension and multiple organ dysfunction between April 2012 and August 2020. Upon admission, the patients were treated with intravenous followed by oral antihypertensive drugs, including RASi and Ca channel blockers (CCB). Kidney function as well as other laboratory and clinical parameters were compared between RASi-treated and CCB- treated group over 2 years. RESULTS: Antihypertensive treatment effectively reduced blood pressure from 222 ± 28/142 ± 21 to 141 ± 18/87 ± 14 mmHg at 2 weeks and eGFR was gradually restored from 33.2 ± 23.3 to 40.4 ± 22.5 mL/min/1.73m2 at 1 year. The renal effect of antihypertensive drugs was particularly conspicuous when RASi was started in combination with other conventional antihypertensive drugs at the early period of hospitalization (2nd day [IQR: 1-5.5]) and even in patients with moderately to severely diminished eGFR (< 30 mL/min/1.73 m2) on admission. In contrast, CCB modestly restored eGFR during the observation period. Furthermore, renal survival probabilities were progressively deteriorated in patients who had manifested reduced eGFR (< 15 mL/min/1.73 m2) or massive proteinuria (urine protein/creatinine ≥ 3.5 g/gCr) on admission. Early use of RASi was associated with a favorable 2-year renal survival probability (0.90 [95%CI: 0.77-1.0] vs. 0.63 [95%CI: 0.34-0.92] for RASi ( +) and RASi (-), respectively, p = 0.036) whereas no apparent difference in renal survival was noted for CCB. CONCLUSIONS: Early use of RASi contributes to the renal functional recovery from acute reduction in eGFR among patients with hypertensive emergencies. Furthermore, RASi offers more favorable effect on 2-year renal survival, compared with CCB.

Surgical procedure and treatment results of pharyngoplasty CWICKs for obstructive sleep apnea.

OBJECTIVE: Uvulopalatopharyngoplasty (UPPP) is performed as a surgical treatment at the oropharyngeal level for obstructive sleep apnea, but there are problems with variations in treatment effects and postoperative complications. Therefore, to improve those, we have devised and put into practice the so-called CWICKs, which is a modified version of barbed reposition pharyngoplasty as a surgical method. We outline the procedure of CWICKs and report the treatment results in comparison with the conventional UPPP. METHODS: CWICKs are surgeries that use resorbable wound closure devices to pull the posterior palatal arch outward and elevate it anteriorly and superiorly to maintain an open upper airway during sleep at the soft palate level. We compared the therapeutic effects of 46 patients evaluated by polysomnography before and after surgery among CWICKs performed in our department between January 2015 and December 2019 and 91 patients who underwent UPPP in our department between January 2000 and December 2008. RESULTS: In 46 patients who underwent CWICKs, significant improvement was observed before and after surgery using the apnea hypopnea index (AHI), obstructive apnea index (OAI), ration of each sleep stage, and SpO2 level > 90%. The improvement rate of AHI was 68.4%, and the surgical success rate was 58.7%. Postoperative patient satisfaction was also good, and significant improvement in subjective sleepiness (Epworth Sleepiness Scale) and subjective sleep quality (Pittsburgh Sleep Quality Index) was observed before and after surgery. No postoperative complications such as dysphagia or scar stenosis were observed in any of the patients in the CWICKs group. Compared with the 91 cases of UPPP, which is the conventional method, there was no significant difference in the improvement rate of AHI (p = 0.199), but the improvement rate of OAI had significantly improved (p = 0.013). Regarding the postoperative sleep stage, In the CWICKs group, a significant decrease in stage 1 and a significant increase in stage 2, stage 3, and stage rapid eye movement were observed, whereas in the UPPP group, no significant improvement in stage 3 was observed. Multivariate analysis of surgical success did not show an association with surgical methods (CWICKs or UPPP). On the other hand, an association was shown with age (<45), palatine tonsil size (≥3 / 5), high MPH (≥14 mm), and OAI rate (> 1/3). CONCLUSION: The treatment outcome of CWICKs was equal to or better than that of the conventional UPPP. Future follow-up is required for long-term prognosis, but no serious postoperative complications, such as dysphagia or scar stenosis, have been observed. CWICKs are considered to be minimally invasive, simple, and effective surgical procedures with few complications.

Chylous Ascites Due to Hyperthyroidism and Heart Failure.

Chylous ascites (CA) is the accumulation of fluid with a high triglyceride content in the peritoneal cavity. Only two cases in the literature have reported CA with hyperthyroidism. A 28-year-old previously healthy woman presented with gradual-onset abdominal swelling, exertional dyspnea, and diarrhea. Hyperthyroidism and heart failure were diagnosed using laboratory investigation and echocardiography. Ultrasonography revealed a large amount of ascites. The ascitic fluid was milky with elevated triglyceride levels. Treatment with anti-thyroid therapy and diuretics improved all symptoms, and the free triiodothyronine (T3) level normalized after five days. Hyperthyroidism and heart failure should be considered as reversible causes of CA.

Ultrafiltration in Japanese critically ill patients with acute kidney injury on renal replacement therapy.

A recent worldwide survey indicates an international diversity in net ultrafiltration (UFNET) practices for the treatment of fluid overload in critically ill patients with acute kidney injury (AKI) requiring renal replacement therapy (RRT). The sub-analysis of the survey has demonstrated that maximum doses of furosemide used before determination of diuretic resistance are lower in Japan than those prescribed worldwide and UFNET is lower but is initiated earlier. In contrast, the interval during which practitioners evaluate fluid balance is longer. The characterization of RRT in critically ill patients in Japan should unveil more appropriate approaches to the successful treatment of AKI.

Role of a rapid response system and code status discussion as determinants of prognosis for critical inpatients: An observational study in a Japanese urban hospital.

ABSTRACT: Rapid response systems (RRS) have been introduced worldwide to reduce unpredicted in-hospital cardiac arrest (IHCA) and in-hospital mortality. The role of advance care planning (ACP) in the management of critical patients has not yet been fully determined in Japan.We retrospectively assessed the characteristics of all inpatients with unpredicted IHCA in our hospital between 2016 and 2018. Yearly changes in the number of RRS activations and the incidence of unpredicted IHCA with or without code status discussion were evaluated from 2014 to 2018. Hospital standardized mortality ratios were assessed from the data reported in the annual reports by the National Hospital Organization.A total of 81 patients (age: 70.9 ±â€Š13.3 years) suffered an unpredicted IHCA and had multiple background diseases, including heart disease (75.3%), chronic kidney disease (25.9%), and postoperative status (cardiovascular surgery, 18.5%). Most of the patients manifested non-shockable rhythms (69.1%); survival to hospital discharge rate was markedly lower than that with shockable rhythms (26.8% vs 72.0%, P < .001). The hospital standardized mortality ratios was maintained nearly constant at approximately 50.0% for 3 consecutive years. The number of cases of RRS activation markedly increased from 75 in 2014 to 274 patients in 2018; conversely, the number of unpredicted IHCA cases was reduced from 40 in 2014 to 18 in 2018 (P < .001). Considering the data obtained in 2014 and 2015 as references, the RRS led to a reduction in the relative risk of unpredicted IHCA from 2016 to 2018 (ie, 0.618, 95% confidence interval 0.453-0.843). The reduction in unpredicted IHCA was attributed partly to the increased number of patients who had discussed the code status, and a significant correlation was observed between these parameters (R2 = 0.992, P < .001). The reduction in the number of patients with end-stage disease, including congestive heart failure and chronic renal failure, paralleled the incidence of unpredicted IHCA.Both RRS and ACP reduced the incidence of unpredicted IHCA; RRS prevents progression to unpredicted IHCA, whereas ACP decreases the number of patients with no code status discussion and thus potentially reducing the patient subgroup progressing to an unpredicted IHCA.

Effects of SGLT2 inhibitors on eGFR in type 2 diabetic patients-the role of antidiabetic and antihypertensive medications.

Recent randomized trials demonstrating the beneficial effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) in type 2 diabetes suggest that early reductions in eGFR upon initiation of SGLT2i therapy are associated with improved renal outcomes. Multiple concomitant medications, including antidiabetic and antihypertensive agents, are commonly used, however, which may modify the renal hemodynamic action of SGLT2is. Here we found that background treatment with metformin diminished the SGLT2i-induced reductions in eGFR after 3 months of SGLT2i therapy in patients with type 2 diabetes and hypertension (-2.29 ± 0.90 vs -5.85 ± 1.27 mL/min/1.73 m2 for metformin users (n = 126) and nonusers (n = 97), respectively). Other antidiabetic agents (DPP4 inhibitors, sulfonylureas and insulin) had no effect on the eGFR response to SGLT2is. Antihypertensive drugs, including calcium channel blockers (CCBs) and ß blockers, did not affect the SGLT2i-induced changes in eGFR, whereas renin-angiotensin system inhibitors (RASis) tended to enhance this response (p = 0.059). Next, we evaluated the interaction between metformin and RASis in the eGFR responses to SGLT2is. Under no background treatment with RASis, metformin abrogated the eGFR response to SGLT2is, but this response was preserved when RASis had been given along with metformin (decreases of 0.75 ± 1.28 vs. 4.60 ± 1.15 mL/min/1.73 m2 in eGFR, p = 0.028). No interaction between metformin and insulin or between metformin and DPP4 inhibitors was observed. In conclusion, metformin blunts the SGLT2i-induced decrease in eGFR, but coadministration of RASis ameliorates this response. Furthermore, the inability of CCBs to modify the SGLT2i-induced reduction in eGFR suggests that the SGLT2i-induced renal microvascular action is mediated predominantly by postglomerular vasodilation rather than preglomerular vasoconstriction.

Net Ultrafiltration Prescription and Practice Among Critically Ill Patients Receiving Renal Replacement Therapy: A Multinational Survey of Critical Care Practitioners.

OBJECTIVES: To assess the attitudes of practitioners with respect to net ultrafiltration prescription and practice among critically ill patients with acute kidney injury treated with renal replacement therapy. DESIGN: Multinational internet-assisted survey. SETTING: Critical care practitioners involved with 14 societies in 80 countries. SUBJECTS: Intervention: MEASUREMENT AND MAIN RESULTS:: Of 2,567 practitioners who initiated the survey, 1,569 (61.1%) completed the survey. Most practitioners were intensivists (72.7%) with a median duration of 13.2 years of practice (interquartile range, 7.2-22.0 yr). Two third of practitioners (71.0%; regional range, 55.0-95.5%) reported using continuous renal replacement therapy with a net ultrafiltration rate prescription of median 80.0 mL/hr (interquartile range, 49.0-111.0 mL/hr) for hemodynamically unstable and a maximal rate of 299.0 mL/hr (interquartile range, 200.0-365.0 mL/hr) for hemodynamically stable patients, with regional variation. Only a third of practitioners (31.5%; range, 13.7-47.8%) assessed hourly net fluid balance during continuous renal replacement therapy. Hemodynamic instability was reported in 20% (range, 20-38%) of patients and practitioners decreased the rate of fluid removal (70.3%); started or increased the dose of a vasopressor (51.5%); completely stopped fluid removal (35.8%); and administered a fluid bolus (31.6%), with significant regional variation. Compared with physicians, nurses were most likely to report patient intolerance to net ultrafiltration (73.4% vs 81.3%; p = 0.002), frequent interruptions (40.4% vs 54.5%; p < 0.001), and unavailability of trained staff (11.9% vs 15.6%; p = 0.04), whereas physicians reported unavailability of dialysis machines (14.3% vs 6.1%; p < 0.001) and costs associated with treatment as barriers (12.1% vs 3.0%; p < 0.001) with significant regional variation. CONCLUSIONS: Our study provides new knowledge about the presence and extent of international practice variation in net ultrafiltration. We also identified barriers and specific targets for quality improvement initiatives. Our data reflect the need for evidence-based practice guidelines for net ultrafiltration.

Challenges in management of unusual acquired factor V deficiency: A case report.

RATIONALE: Acquired inhibitors of coagulation are antibodies that either inhibit the activity or increase the clearance of a clotting factor. Acquired factor V deficiency is a rare coagulation disorder, and it can sometimes be life threatening. PATIENT CONCERNS: We describe a case of a 90-year-old Japanese male with acquired factor V deficiency. He was previously misdiagnosed with congenital factor V deficiency when he presented with hemoptysis and a negative factor V inhibitor test result at a different hospital 5 years earlier. Coagulopathy recurred with ecchymosis when he sustained a bruise after falling on a bush. DIAGNOSIS: Although the factor V inhibitor test result was negative and a mixing study suggested a deficiency pattern, we diagnosed the patient with acquired factor V deficiency on the basis of no history of bleeding diathesis, a lack of response to multiple fresh frozen plasma transfusion, and clinical response to corticosteroid therapy. INTERVENTIONS: Intravenous methylprednisolone was administered at 500 mg/day for 3 days, followed by oral prednisolone at 1 mg/kg/day. OUTCOMES: Coagulation test results improved and symptoms resolved 2 weeks after corticosteroid administration. LESSONS: This case report suggests that clearance-facilitating antibodies exist without the presence of neutralizing inhibitors. When patients present with coagulation factor V deficiency in the absence of coagulation inhibitors, acquired factor V deficiency should also be considered.

Difficulty of acute hepatitis C diagnosis in a hospitalised patient.

The hepatitis C virus (HCV) causes acute hepatitis C and is commonly detected via HCV antibody testing. However, delayed seroconversion of HCV antibodies and non-specific symptoms may hinder the diagnosis of this disease. A 71-year-old woman developed acute hepatitis while hospitalised for back pain. An HCV antibody test was negative, and she had no risk factors for hepatitis C. She was referred to our hospital for further evaluation. The HCV antibody test was repeated 16 days after the initial test; owing to a positive result, she was diagnosed with acute hepatitis C. Several months thereafter, the HCV spontaneously cleared. When diagnosing an HCV infection, the time at which the testing is performed needs to coincide with the time at which HCV antibody seroconversion occurs. Timely diagnosis of an HCV infection allows appropriate treatment during the acute phase which may prevent disease progression to the chronic phase.

Role of dental sleep medicine in management of patients with obstructive sleep apnea disorders using a team approach.

OBJECTIVE: Obstructive sleep apnea (OSA) is a significant social and health issue. An integrated multidisciplinary approach to OSA management may be the most effective owing to its multifactorial etiology. In this study, we evaluated the frequency and efficacy of various treatment modalities for OSA administered via an integrated care delivery model, and assessed the role of dental sleep medicine as part of a multidisciplinary team. MATERIALS AND METHODS: We retrospectively evaluated 1115 patients with OSA treated at the Tokyo Medical University Hospital's Outpatient Clinic for OSA by a multidisciplinary team under one roof. The various treatment methods included the following: continuous positive airway pressure (CPAP), oral appliance (OA), surgery, and behavioral treatment. RESULTS: The patient number of study group was as follows: 771 (69.1%) CPAP; 240 (21.5%) OA; 76 (6.8%) behavioral treatment and 28 (3%) surgery. Because significantly fewer patients underwent surgery, there was a discrepancy between the recommended first-choice treatment and the actual treatment. A statistically significant number of younger patients in each treatment group underwent surgery. Success rate of OA and MMA were 74.4 and 80%, respectively. CONCLUSIONS: Proper selection of primary treatment to manage patients with OSA was possible under one-roof system that included dental sleep medicine.

Expression and subcellular localisation of AID and APOBEC3 in adenoid and palatine tonsils.

Activation-induced cytidine deaminase (AID) and apolipoprotein B mRNA-editing catalytic polypeptide 3 (A3) family are cytidine deaminases that play critical roles in B-cell maturation, antiviral immunity and carcinogenesis. Adenoids and palatine tonsils are secondary lymphoid immune organs, in which AID and A3s are thought to have several physiological or pathological roles. However, the expression of AID or A3s in these organs has not been investigated. Therefore, we investigated the expression profiles of AID and A3s, using 67 samples of adenoids and palatine tonsils from patients, with reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemical analyses. AID and A3s expression levels in the adenoids and the palatine tonsils of the same individual significantly correlated with each other. Of note, AID expression level in the adenoids negatively correlated with the age (r = -0.373, P = 0.003). The younger group with adenoid vegetation and tonsillar hypertrophy showed more abundant AID expression than the older group with recurrent tonsillitis and peritonsillar abscesses (P = 0.026). Moreover, immunohistochemical analysis revealed the distribution of AID and A3s in the epithelial cells as well as germinal centres. The localisation of AID expression and its relation to age may contribute to adenoid vegetation and inflammation.

APOBEC3G is increasingly expressed on the human uterine cervical intraepithelial neoplasia along with disease progression.

PROBLEM: APOBEC3G (A3G) is a cytidine deaminase that exhibits antiviral activity by introducing C-to-T hypermutation in viral DNA. We recently observed the distinct presence of C-to-T hypermutation of human papillomavirus DNA in uterine cervical intraepithelial neoplasia (CIN), suggesting the possible involvement of A3G in the mutation-inducing process. Consequently, we investigated the association of A3G expression with CIN progression in this study. METHOD OF STUDY: Patients who had undergone cervical conization due to CIN1 (n=11), CIN2 (n=9), CIN3 (n=12), and micro-invasive squamous cell carcinoma (n=2) were included. The expression profiles of A3G and p16 proteins in cervical lesions and A3G-positive immune cells around the lesions were examined by immunohistochemistry. RESULTS: Immunoreactive A3G protein was detected in the CIN and squamous cell carcinoma lesions. Its expression intensity and positive areas were increased and spread in accordance with the progression of CIN, respectively. The co-expression of p16 was observed on the A3G-positive atypical cells. The numbers of A3G-positive immune cells in CIN3 lesions were significantly higher than those of CIN1-2 lesions. CONCLUSION: These findings indicate that A3G is associated with CIN, suggesting its important roles in human papillomavirus-induced pathophysiological processes such as CIN progression and viral elimination.

Radiological improvement by tocilizumab in polyarticular juvenile idiopathic arthritis.

Recent advances in biologic therapy have enabled reduction of the progression of destructive arthritis in rheumatoid arthritis. Once destroyed, however, the affected bones and cartilage are not fully repaired. We describe the case of an 8-year-old girl with anti-citrullinated peptide antibody (ACPA)-positive polyarticular juvenile idiopathic arthritis (p-JIA). Destructive arthritis progressed during combination therapy with infliximab, methotrexate, mizoribine and prednisolone. Clinical remission was achieved, however, after switching the biologic agent to tocilizumab, a humanized monoclonal antibody to interleukin-6 receptor. Both bone erosion and bone marrow edema on magnetic resonance imaging were repaired in association with restoration of joint spaces. Furthermore, there was no relapse of arthritis on weekly methotrexate alone for 2 years after discontinuation of the tocilizumab. Tocilizumab led to radiological repair of both bone and cartilage destruction and long-term biologics-free remission in a patient with ACPA-positive p-JIA, and should be considered for tumor necrosis factor inhibitor-resistant cases.

[The efficacy of genioglossus advancement and uvulopalatopharyngoplasty for obstructive sleep apnea syndrome].

OBJECTIVE: To evaluate the objective and subjective improvement after multilevel surgery, genioglossus advancement (GA) plus uvulopalatopharyngoplasty (UPPP) for the treatment of obstructive sleep apnea syndrome (OSAS). METHODS: GA and UPPP were undertaken in 24 patients with moderate and severe OSAS between January 2006 and December 2011. Epworth Sleepiness Scale (ESS) score, snoring, the feeling of having slept well and polysomnography were used for the evaluation of surgical outcomes. In addition, we determined whether baseline polysomnography, cephalometry, and authropometry data could predict GA and UPPP success or failure. RESULTS: The mean ESS score decreased significantly from 12.96 to 7.08. The mean apnea-hypopnea index (AHI) improved from 37.3 to 19.33. Objective success as evaluated by a 50% reduction in AHI or by AHI < 15 was obtained in 16 of 24 patients. The lowest oxygen saturation and stage 1 and stage 2 were also improved significantly. There were no major postoperative complications. There were significant differences in SNA, SNB, FX and PNS-P between the success and failure of GA and UPPP. The indication of GA and UPPP were SNA > 79.11 degrees, SNB > 75.69 degrees, FX > 78.67 degrees, and 36.79 mm < PNS-P < 42.29 mm. CONCLUSION: GA and UPPP surgeries are effective and safe for patients with moderate and severe OSAS. However, further studies are necessary to decide definitively if GA and UPPP are appropriate treatments for OSAS.