Data-driven prediction models for forecasting multistep ahead profiles of mammalian cell culture toward bioprocess digital twins.

Recently, the advancement in process analytical technology and artificial intelligence (AI) has enabled the generation of enormous culture data sets from biomanufacturing processes that produce various recombinant therapeutic proteins (RTPs), such as monoclonal antibodies (mAbs). Thus, now it is very important to exploit them for the enhanced reliability, efficiency, and consistency of the RTP-producing culture processes and for the reduced incipient or abrupt faults. It is achievable by AI-based data-driven models (DDMs), which allow us to correlate biological and process conditions and cell culture states. In this work, we provide practical guidelines for choosing the best combination of model elements to design and implement successful DDMs for given hypothetical in-line data sets during mAb-producing Chinese hamster ovary cell culture, as such enabling us to forecast dynamic behaviors of culture performance such as viable cell density, mAb titer as well as glucose, lactate and ammonia concentrations. To do so, we created DDMs that balance computational load with model accuracy and reliability by identifying the best combination of multistep ahead forecasting strategies, input features, and AI algorithms, which is potentially applicable to implementation of interactive DDM within bioprocess digital twins. We believe this systematic study can help bioprocess engineers start developing predictive DDMs with their own data sets and learn how their cell cultures behave in near future, thereby rendering proactive decision possible.

Synthesis and Characterization of Poly(Butylene Sebacate-Co-Terephthalate) Copolyesters with Pentaerythritol as Branching Agent.

Poly(butylene sebacate-co-terephthalate) (PBSeT) copolyesters are prepared by melt polymerization via two-step transesterification and polycondensation using pentaerythritol (PE) as a branching agent. The effects of the incorporated PE on its chemical, thermal, mechanical, and degradation properties, along with the rheological properties of its melt, are investigated. The highest molecular weight and intrinsic viscosity along with the lowest melt flow index were achieved at a PE content of 0.2 mol%, with minimal reduction in the tensile strength and the highest tear strength. The addition of PE did not significantly influence the thermal behavior and stability of the PBSeT copolyesters; however, the elongation at break decreased with increasing PE content. The sample with 0.2 mol% PE exhibited a higher storage modulus and loss modulus as well as a lower loss angle tangent than the other samples, indicating improved melt elasticity. The incorporation of more than 0.2 mol% PE enhanced the enzymatic degradation of copolyesters. In summary, including within 0.2 mol%, PE effectively improved both the processability-related characteristics and degradation properties of PBSeT copolyesters, suggesting their potential suitability for use in agricultural and packaging materials.

Serum biomarkers for bisphosphonate-related osteonecrosis of the jaw: a prospective clinical study.

In this prospective study, serum levels of 12 possible biomarkers were compared between osteonecrosis of the jaw (ONJ) and control groups, before and after dentoalveolar surgery. The results suggest that patients with abnormal serum levels of specific biomarkers should be monitored closely for the prevention and early diagnosis of ONJ. INTRODUCTION: Bisphosphonate-related osteonecrosis of the jaw (ONJ) is an adverse effect of long-term bisphosphonate therapy. This study aimed to identify bone biomarkers for ONJ risk assessment and diagnosis. METHODS: This prospective study included patients with histories of bisphosphonate therapy without current ONJ who were in need of dentoalveolar surgery of the jaw area. Serum levels of 12 possible bone markers, selected based on their involvement in ONJ pathogenesis, were compared between ONJ and control groups before dentoalveolar surgery (T0), at 8 postoperative weeks (T1), and at 4 months after diagnosis(T2). RESULTS: Seventy-six patients who met the inclusion criteria were included in the study; 33 were assigned to the ONJ group, and 43 patients without ONJ signs or symptoms after dentoalveolar surgery were assigned to the control group. In the ONJ group, at both T0 and T1, the mean tartrate-resistant acid phosphatase isoform 5b (TRACP 5b) levels were significantly lower and the mean Dickkopf-related protein 1 (DKK1) levels were significantly higher than the corresponding values for the control group. Linear mixed model analysis revealed significant group effects over time for serum TRACP 5b and DKK1 after adjusting for demographic, pharmacological, and diagnostic variables. Lower serum levels of TRACP 5b under a specified cut-off value (≤ 2.899 U/L) at T0 indicated a 20.40-fold increased risk of ONJ development. CONCLUSION: Patients with abnormally low serum levels of TRACP 5b and high serum levels of DKK1 should be monitored closely before and after dentoalveolar surgery for the prevention and early diagnosis of ONJ.

Recovery from chronic periodontal disease is associated with lower risk for incident diabetes.

AIM: The presence of periodontal disease (PD) at a single time point has been suggested as a predictor of diabetes risk, but whether changes in PD status are associated with altered risk of diabetes is yet to be reported on a population scale. This study investigated whether recovery from or development of PD in a population is associated with an altered risk of diabetes occurrence. MATERIALS AND METHODS: Data of subjects who received health screening from 2002 to 2007 were obtained from the National Health Insurance Service-National Health Screening cohort database of Korea. Patients with a history of diabetes were excluded. Changes in PD status were determined from the first two health screenings. Study subjects were divided into four groups according to the changes in PD status: PD-free, PD-recovered, PD-developed, and PD-chronic. The outcome was the occurrence of diabetes. RESULTS: Overall, 111,611 subjects were included for analysis. During a median follow-up of 9.10 years, diabetes developed in 6102 subjects. The adjusted hazard ratios (HRs) for incident diabetes across various PD change groups (in reference to the PD-free group) were as follows: PD-chronic group = 1.096 (95% confidence interval [CI] 1.026-1.170, p = .006); PD-developed group = 1.073 (95% CI 0.993-1.159, p = .075); and PD-recovered group = 1.019 (95% CI 0.945-1.100, p = .622). The subjects who recovered from PD had a lower diabetes risk than those who had consistent PD (adjusted HR 0.930, 95% CI 0.865-1.000, p = .050), whereas those who developed PD had a higher risk of diabetes than those who remained PD-free. CONCLUSION: The longitudinal change in PD status is associated with incident diabetes risk. Future intervention studies are necessary to determine whether PD treatment can prevent incident diabetes.

Maleic Anhydride-Grafted PLA Preparation and Characteristics of Compatibilized PLA/PBSeT Blend Films.

Poly(butylene sebacate-co-terephthalate) (PBSeT) is a biodegradable flexible polymer suitable for melt blending with other biodegradable polymers. Melt blending with a compatibilizer is a common strategy for increasing miscibility between polymers. In this study, PBSeT polyester was synthesized, and poly(lactic acid) (PLA) was blended with 25 wt% PBSeT by melt processing with 3-6 phr PLA-grafted maleic anhydride (PLA-g-MAH) compatibilizers. PLA-g-MAH enhanced the interfacial adhesion of the PLA/PBSeT blend, and their mechanical and morphological properties confirmed that the miscibility also increased. Adding more than 6 phr of PLA-g-MAH significantly improved the mechanical properties and accelerated the cold crystallization of the PLA/PBSeT blends. Furthermore, the thermal stabilities of the blends with PLA-g-MAH were slightly enhanced. PLA/PBSeT blends with and without PLA-g-MAH were not significantly different after 120 h, whereas all blends showed a more facilitated hydrolytic degradation rate than neat PLA. These findings indicate that PLA-g-MAH effectively improves PLA/PBSeT compatibility and can be applied in the packaging industry.

Medication-related osteonecrosis of the maxilla: Prognosis of oral surgery combined with endoscopic sinus surgery.

OBJECTIVES: To evaluate the effect of functional endoscopic sinus surgery (FESS) on the resolution of maxillary medication-related osteonecrosis of the jaw (MRONJ). PATIENTS AND METHODS: This study included 62 patients diagnosed with MRONJ in the maxillary posterior area with or without maxillary sinusitis (MS). All patients underwent oral surgery. The concomitant MS was evaluated, and if indicated, FESS was performed on the same operation. Follow-up included clinical and radiological examinations at 4 months postoperation. RESULTS: Of the 62 patients, 24 (38.7%) showed no evidence of MS and 38 (61.3%) showed MS. Advanced MRONJ (stage 3), which has bony destruction of the sinus floor and signs of MS according to its definition, was seen in 27 patients (43.5%). In stage 3 MRONJ, patients with combined treatment of oral surgery and FESS compared to those treated with oral surgery alone showed higher percentage of resolution (84.2%, 37.5%, respectively) at 4 months postoperatively, and the results were statistically significant. CONCLUSION: Simultaneous management of MRONJ and sinusitis with combined treatment of oral surgery and FESS for the treatment of maxillary MRONJ can be an effective method, especially for advanced cases, to address its associated lesions.

Can ultrasonography be used to assess capsular distention in the painful temporomandibular joint?

BACKGROUND: To determine whether capsular distention in the painful temporomandibular joint (TMJ) can be assessed by ultrasonography, we compared the capsular width between painful TMJs and painless TMJ. The risk factors for TMJ pain were also investigated including capsular width and other clinical factors such as TMJ sounds that may affect the occurrence and persistence of TMJ pain. METHODS: TMJ ultrasonography was performed on 87 temporomandibular disorder (TMD) patients, including 47 unilateral and 29 bilateral TMJ pain patients, and 11 patients without TMJ pain. RESULTS: The capsular width was greater in the 105 painful joints than in the 69 painless joints. Considering individual anatomical variations, the differences between painful and painless joints in unilateral TMJ pain patients were also analyzed, revealing a greater width in painful joints. Capsular width was a risk factor for TMJ pain with an adjusted odds ratio of 1.496 (95% confidence interval 1.312-1.706; p < 0.001) and was significantly correlated with pain scores. CONCLUSION: This correlation may suggest that pain intensity is associated with widened capsular width because of joint effusion or synovitis. Further studies are required to refine and establish the protocols for standard examinations using ultrasound imaging.

Long-term clinical course and outcomes of immunoglobulin G4-related lung disease.

BACKGROUND: Immunoglobulin G4-related lung disease (IgG4-RLD) is the pulmonary manifestation of a systemic fibroinflammatory disease characterized by lymphoplasmacytic infiltration with an abundance of IgG4-positive plasma cells. Long-term clinical course and outcomes of IgG4-RLD remain unclear. We aimed to identify clinical characteristics, treatment outcomes, and longitudinal pulmonary function changes in patients with IgG4-RLD according to the radiologic classification. METHODS: Chest computed tomography findings of 37 subjects were classified into five subtypes: solid nodular, bronchovascular, alveolar interstitial, round ground glass opacity, and alveolar consolidative. Radiologic treatment outcomes and longitudinal pulmonary function changes were compared among the different radiologic subtypes. RESULTS: The mean age of the subjects was 55.6 years, and 78.4% were male. Among the five radiologic subtypes, alveolar consolidative and solid nodular type were most common, accounting for approximately 29.7% each of the total cases. Prednisone with or without azathioprine was administered to 31 patients (median treatment duration 14 months). In the treated patients, serial images showed complete response or partial response in 77.4%. However, relapse was documented in 25.0% of those who showed complete or partial response. In patients whose longitudinal lung function data were available (n = 20), the lung function was found to be stable during follow-up. Alveolar consolidative type showed the highest complete response rate, whereas alveolar interstitial type showed the lowest response rate, either complete or partial. CONCLUSIONS: Most patients showed a favorable outcome with regards to radiologic improvement and maintenance of pulmonary function; however, the response differed according to the radiologic subtype.

Soft tissue expander for vertically atrophied alveolar ridges: Prospective, multicenter, randomized controlled trial.

OBJECTIVES: Conventional guided bone regeneration (GBR) limits the amount of bone graft due to limited soft tissue expansion. We hypothesize that the use of tissue expander will successfully augment soft tissue prior to bone graft, allowing for sufficient amount of grafting which will lead to a more stable and effective vertical bone graft. The authors aimed to evaluate effectiveness of the novel self-inflating tissue expander for vertical augmentation in terms of soft tissue expansion, clinical outcomes, and related complications. MATERIAL AND METHODS: A prospective, multicenter, randomized controlled trial was performed on patients requiring vertical augmentation. For experimental group patients, the tissue expander was subperiosteally implanted and followed by a tunneling bone graft without full flap reflection. Control patients underwent conventional vertical GBR. Primary objectives were to evaluate the dimensional changes of soft tissue and radiographic vertical bone gain and retention. As a secondary outcome, clinical complications and thickness changes of expanded overlying tissue were assessed and analyzed. RESULTS: Twenty-three patients in each group were included. During a 4-week expansion, two of the experimental group showed over-expansion and one showed mucosal perforation associated with previous severe scars. The other patients showed uneventful expansion and mean tissue augmentation was 6.88 ± 1.64 mm vertically. Ultrasonographic measurements of overlying gingiva revealed no thinning after tissue expansion (p > .05). Significantly higher vertical bone gain was shown in the experimental group (5.12 ± 1.25 mm) compared with that in the control patients (4.22 ± 1.15 mm; p < .05). After a 6-month retention period, the mean vertical bone measurement of the controls had decreased to 1.90 mm (55.0% reduction), which was a significantly greater decrease than that in the experimental group (mean 3.55 mm, 30.7% reduction; p < .05). CONCLUSION: Our results demonstrated the effectiveness of tissue expanders followed by tunneling bone graft for vertical augmentation; however, studies comparing the two techniques without tissue expanders are needed to elucidate the net effect of tissue expansion.

Randomized controlled trial on the effectiveness of absorbable collagen sponge after extraction of impacted mandibular third molar: split-mouth design.

BACKGROUND: The purpose of this study was to compare the effectiveness of absorbable collagen sponge insertion in tooth extraction sites for socket healing of the impacted mandibular third molar. METHODS: Thirty-six patients with bilateral mandibular impacted third molars based on Pell-Gregory and Winter classification were included in this study. This study was a randomized clinical trial utilizing a split-mouth design with one side assigned as collagen sponge insertion and the other side assigned as the control. Post-operative clinical complications, periodontal integrities, and radiographic outcomes were assessed at 1, 2, and 14-weeks post operatively. RESULTS: Five patients were excluded during the follow-up period due to loss of follow-up. The study was conducted on 31 patients in total. The mean VAS score of collagen sponge insertion side at 1 week post operation was 1.42 ± 1.26, which was significantly lower than the control side (P < 0.05). The mean probing depth of collagen sponge insertion side at 2-week post operation was 5.55 ± 2.28 mm, which was significantly lower than the control side (7.13 ± 1.86; P < 0.05). Other various measurements including radiographic outcomes showed no significant group differences. CONCLUSIONS: Placement of collagen sponge after extraction of mandibular impacted third molar reduced early stage post-operative complications and enhanced initial healing of soft tissues and periodontal defects. TRIAL REGISTRATION: This study was retrospectively registered at the WHO ICTRP platform and Clinical Research Information Service, KCT0003363. Registered 21 Sep 2018.

Traumatic Buccal Fat Pad Herniation in Young Children: A Systematic Review and Case Report.

PURPOSE: Traumatic herniation of a buccal fat pad, predominantly seen in young children, is a rare condition. Because of its rarity and clinical features that resemble tumors, clinicians are faced with challenges at the initial diagnosis. This report describes a case of buccal fat pad herniation with excellent long-term prognosis after surgical relocation and conservative treatment and presents a systematic review of the literature on its management. MATERIALS AND METHODS: Through a PubMed search, 811 articles were initially identified. Case series, case reports, technical notes, case and review reports, and retrospective case series were included. After screening and manual review, the sample was narrowed to 35 reports (41 patients) based on eligibility criteria. Articles were included if the standard criteria for traumatic intraoral herniation of buccal fat pad were met. RESULTS: Patients' ages ranged from 4 months to 12 years, with no specific gender predilection. Management consisted of excision (82.9%), relocation (14.6%), and observation (2.4%). Follow-up ranged from 1 week to 4 months. No reports presented a follow-up longer than 4 months; hence, data on long-term prognosis were not reported. For the present case report, a 19-month-old boy diagnosed with traumatic buccal fat pad herniation was successfully treated with surgical relocation and antibiotic support. Twelve-month follow-up showed no esthetic or functional disturbance or recurrence. CONCLUSION: Traumatic herniation of the buccal fat pad requires special attention at the initial diagnosis. Considering its clinical importance in young children and few studies have reported long-term postresection follow-up, surgical relocation can be regarded as an excellent and more conservative treatment option.

Does the Addition of Bone Morphogenetic Protein 2 to Platelet-Rich Fibrin Improve Healing After Treatment for Medication-Related Osteonecrosis of the Jaw?

PURPOSE: To investigate the effect of the addition of bone morphogenetic protein 2 (BMP-2) to leukocyte-rich and platelet-rich fibrin (L-PRF) on the treatment of medication-related osteonecrosis of the jaws (MRONJ), this study compared the healing outcome of combined use of BMP-2 and L-PRF with single use of L-PRF. PATIENTS AND METHODS: Of 55 patients who were diagnosed with MRONJ, 25 were treated with L-PRF alone and 30 were treated with L-PRF and recombinant human BMP-2. For each patient, surgical sites were evaluated postoperatively at 4 and 16 weeks. Associations between the treatment method and the resolution of MRONJ were analyzed with the adjustment of patient-specific factors that may influence the treatment outcome. RESULTS: At 4 and 16 weeks postoperatively, patients with MRONJ who were treated with both L-PRF and BMP-2 showed favorable outcomes with complete resolution of the lesions, which was statistically significant compared with that of the therapy using L-PRF alone (P = .028). Therefore, the additional use of BMP-2 considerably improved MRONJ healing. Among patient-specific factors, the existence of a bacterial colony in the biopsy specimen was a significant factor that negatively affected disease resolution (P = .017). CONCLUSIONS: The combined use of BMP-2 and L-PRF leads to the early resolution of MRONJ; thus patients who need to continue antiresorptive therapy may benefit from the combined regimen.

Role of microcracks in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw.

OBJECTIVES: The aim of this study was to investigate the potential role of microcrack accumulation in the pathogenesis of bisphosphonate-related osteonecrosis of the jaw (ONJ) through an animal model. MATERIALS AND METHODS: Twenty-four ovariectomized rats were randomly divided into a bisphosphonate group (n = 19) and control group (n = 5) and weekly injected with zoledronic acid and normal saline, respectively. After 6 weeks, surgical intervention was performed, and the injections were continued for eight additional weeks. Then, the animals were sacrificed, and ONJ lesions were inspected for the presence of microcracks using scanning electron microscopy. Measurements included bone dimension, number of cracks, crack length, and normalized indices; crack density (Cr.Dn) and crack surface density (Cr.S.Dn) were used for group comparison. RESULTS: Both number of cracks and crack length in the bisphosphonate group were greater than those in the control group (P < 0.05). Of the 19 rats injected with bisphosphonates, 13 rats (68.4 %) were classified into the ONJ group. Cr.Dn and Cr.S.Dn were significantly greater in the ONJ group than in the non-ONJ group, indicating accumulation of unrepaired microcracks (P < 0.05). Seventy-two percent of microcracks in the ONJ group conformed to the defined length that was considered significant according to a previous literature (30-80 µm); whereas 12 % of microcracks in the non-ONJ group were considered significant (P < 0.05). CONCLUSION: Accumulation of unrepaired microcracks was significantly associated with the development of bisphosphonate-related ONJ. Further research is required to determine the role of microcracks in the pathogenesis of bisphosphonate-related ONJ. CLINICAL RELEVANCE: Long-term bisphosphonates use may deteriorate the biomechanical and physiological bone integrity, contributing to the pathogenesis of bisphosphonate-related ONJ.

Midfacial Soft-Tissue Changes after Paranasal Augmentation with Porous Polyethylene.

The aim of this study was to determine the effect of porous polyethylene in paranasal augmentation on the overlying soft tissue. Thirty-three patients underwent paranasal augmentation using 3-mm-thick porous polyethylene and mandibular setback, and 35 patients underwent mandibular setback only. Lateral cephalograms were taken before and 6 months after the surgery to compare the soft-tissue changes in the paranasal area. Complications and patient satisfaction following the surgery were also analyzed. The average soft-tissue change in the paranasal area after the augmentation was 2.42 ± 0.33 mm, while there was no definite soft-tissue change in the paranasal area after mandibular setback alone. The ratio of soft-tissue changes to paranasal implant thickness was 80.7%. All patients in the augmentation group were satisfied with their surgical outcomes, which led to convex lateral profile with increase in midface volume. There were no complications such as postoperative infection or foreign body reaction requiring removal of implants. Paranasal augmentation using porous polyethylene is a predictable method providing minimal morbidity in patients with paranasal deficiency.

Perceptions of medical doctors on bisphosphonate-related osteonecrosis of the jaw.

BACKGROUND: This study aimed to investigate medical doctors' awareness of bisphosphonate-related osteonecrosis of the jaw (BRONJ) and the status of dental referrals. METHODS: Self-administered questionnaires were distributed to medical doctors practicing internal medicine, family medicine, and orthopedics at the 6 tertiary medical centers located in Seoul, Korea. The survey consisted of 22 questions regarding the general characteristics, bisphosphonate therapy, awareness of BRONJ, and implementation of dental referrals. RESULTS: Among 192 medical doctors, 21.9 % had not heard of the disease. Only 8.9 % correctly answered all 5 questions testing BRONJ knowledge. Dental referrals made by medical doctors were implemented in less than 30 % of the total patients. Oncology specialists most often recognized the necessity of dental referrals followed in decreasing order by endocrinology, rheumatology, family medicine, and orthopedic specialists. CONCLUSION: Given medical doctors' low BRONJ perception and implementation level of dental referrals, enhancing information dissemination on BRONJ and development of a highly accessible educational program recognizing the need for dental referrals are urgent.

Ethical issues recognized by critical care nurses in the intensive care units of a tertiary hospital during two separate periods.

This research aimed to investigate the changes in ethical issues in everyday clinical practice recognized by critical care nurses during two observation periods. We conducted a retrospective analysis of data obtained by prospective questionnaire surveys of nurses in the intensive care units (ICU) of a tertiary university-affiliated hospital in Seoul, Korea. Data were collected prospectively during two different periods, February 2002-January 2003 (Period 1) and August 2011-July 2012 (Period 2). Significantly fewer cases with ethical issues were reported in Period 2 than in Period 1 (89 cases [2.1%] of 4,291 ICU admissions vs. 51 [0.5%] of 9,302 ICU admissions, respectively; P < 0.001). The highest incidence of cases with identified ethical issues in both Periods occurred in MICU. The major source of ethical issues in Periods 1 and 2 was behavior-related. Among behaviorrelated issues, inappropriate healthcare professional behavior was predominant in both periods and mainly involved resident physicians. Ethical issue numbers regarding end-oflife (EOL) care significantly decreased in the proportion with respect to ethical issues during Period 2 (P = 0.044). In conclusion, the decreased incidence of cases with identified ethical issues in Period 2 might be associated with ethical enhancement related with EOL and improvements in the ICU care environment of the studied hospital. However, behaviorrelated issues involving resident physicians represent a considerable proportion of ethical issues encountered by critical care nurses. A systemic approach to solve behavior-related issues of resident physicians seems to be required to enhance an ethical environment in the studied ICU.

Condylar positional changes up to 12 months after bimaxillary surgery for skeletal class III malocclusions.

PURPOSE: Postsurgical changes in the condylar position are of great importance to surgical stability, especially in asymmetric double-jaw surgery. The aims of this study were to evaluate positional changes of the condyle up to 12 months after surgery in patients with Class III malocclusion and to identify the factors affecting postsurgical condylar position. MATERIALS AND METHODS: The study included 33 adult patients diagnosed with skeletal Class III malocclusion who underwent bimaxillary surgery and had full cone-beam volumetric imaging (CBVI) records up to 1 year after surgery. The CBV images were obtained before surgery and 2 weeks, 3 months (T2), 6 months (T3), and 12 months after surgery. Condyles with deviated and nondeviated sides were examined separately regardless of the degree of asymmetry. Analyses of variance and multiple regression analysis were performed to identify factors that could affect the position of the mandibular condyles. RESULTS: The condyles exhibited anterior displacement at T2, which returned to a more distal position afterward in the axial view, and an inward rotation in the coronal view up to T3. From the sagittal view, the deviated and nondeviated condylar sides rotated forward and remained stable after T2. The degree of menton deviation affected the angle of condylar rotation (horizontal angle). CONCLUSION: The results of this study suggest that condyles tend to move in a certain direction, and this can influence postsurgical relapse up to 6 months after surgery. However, they remain relatively stable afterward.

Optimizing third molar autotransplantation: applications of reverse-engineered surgical templates and rapid prototyping of three-dimensional teeth.

The success of autogenous tooth transplantation depends on the vitality of the periodontal ligament attached to the donor tooth, and its viability decreases when it is exposed extraorally. This report describes the case of a 16-year-old patient in whom a rapid prototyped tooth model was performed using cone-beam technology and a surgical template guide for autotransplantation as an effective technique for a critical time-based procedure.

Prevention of venous thromboembolism in medical intensive care unit: a multicenter observational study in Korea.

Patients admitted to medical intensive care unit (MICU) are at increased risk for venous thromboembolism (VTE); and prophylaxis is recommended. However, the actual range and frequency of VTE prophylaxis administered to MICU patients are not well defined. Patients over 40 yr of age and expected MICU stay of more than 48 hr were eligible for this observational cohort study of 23 MICUs in Korea. Patients already on anticoagulation therapy or those requiring anticoagulation for reasons other than VTE were excluded. Among 830 patients, VTE prophylaxis was given to 560 (67.5%) patients. Among 560 patients, 323 (38.9%) received pharmacoprophylaxis, 318 (38.4%) received mechanical prophylaxis and 81 (9.8%) received both forms of prophylaxis. About 74% of patients in the pharmacoprophylaxis group received low molecular weight heparin and 53% of the patients in the mechanical prophylaxis group used intermittent pneumatic compression. Most of the patients (90%) had more than one risk factor for VTE and the most common risk factor was old age, followed by heart and respiratory failure. In this observational cohort study of 23 MICUs in Korea, 67.5% of patients received thromboprophylaxis. Further studies are needed to clarify the role and efficacy of VTE prophylaxis in Korean critically ill patients.

Adjunctive recombinant human parathyroid hormone agents for the treatment of medication-related osteonecrosis of the jaw: a report of three cases.

Teriparatide has been effective in treating people diagnosed with medication-related osteonecrosis of the jaw (MRONJ). However, its efficacy is not well established to be accepted as a standard of care. The objective of this paper was to investigate the efficacy of recombinant human parathyroid hormone for the treatment of MRONJ. We report three cases of MRONJ patients with osteoporosis as the primary disease who were treated with a teriparatide agent along with other adjunctive measures. Each patient was administered a teriparatide injection subcutaneously for 16 weeks, 36 weeks, or 60 weeks. Surgical intervention including partial resection, sequestrectomy, decortication, and saucerization took place during the teriparatide administration. Complete lesion resolution was identified clinically and radiographically in all three patients. In patients diagnosed with MRONJ, teriparatide therapy is an efficacious and safe therapeutic option to improve healing of bone lesions. These findings demonstrate that teriparatide in combination with another therapy, especially bone morphogenetic protein, platelet-rich fibrin, or antibiotic therapy, can be an effective protocol for MRONJ.