Evaluating Novel SP-B and SP-C Synthetic Analogues for Pulmonary Surfactant Efficacy.

Pulmonary surfactants, a complex assembly of phospholipids and surfactant proteins such as SP-B and SP-C, are critical for maintaining respiratory system functionality by lowering surface tension (ST) and preventing alveolar collapse. Our study introduced five synthetic SP-B peptides and one SP-C peptide, leading to the synthesis of CHAsurf candidates (CHAsurf-1 to CHAsurf-5) for evaluation. We utilized a modified Wilhelmy balance test to assess the surface tension properties of the surfactants, measuring spreading rate, surface adsorption, and ST-area diagrams to comprehensively evaluate their performance. Animal experiments were performed on New Zealand white rabbits to test the efficacy of CHAsurf-4B, a variant chosen for its economic viability and promising ST reduction properties, comparable to Curosurf®. The study confirmed that higher doses of SP-B in CHAsurf-4 are associated with improved ST reduction. However, due to cost constraints, CHAsurf-4B was selected for in vivo assessment. The animal model revealed that CHAsurf-4B could restore alveolar structure and improve lung elasticity, akin to Curosurf®. Our research highlights the significance of cysteine residues and disulfide bonds in the structural integrity and function of synthetic SP-B analogues, offering a foundation for future surfactant therapy in respiratory disorders. This study's findings support the potential of CHAsurf-4B as a therapeutic agent, meriting further investigation to solidify its role in clinical applications.

Is the occurrence of extra-articular calcaneal fractures of the joint depression type related to osteoporosis and aging?

PURPOSE: The authors experienced several cases of extra-articular calcaneal fracture accompanied by joint depression involving the entire posterior facet without joint involvement. This type of fracture and its characteristics and treatment outcomes have not been previously reported. The study was performed to analyze the characteristics of extra-articular calcaneal fractures of the joint depression type and their postoperative clinical and radiographic results and complications. METHODS: Between February 2013 and March 2021, 23 extra-articular calcaneal fractures of the joint depression type were consecutively treated by a single surgeon. Relationships between fracture characteristics and patient demographics were assessed. Clinical results were quantified using visual analog scale, American Orthopaedic Foot and Ankle Society ankle-hindfoot scale, and Foot Function Index, radiographic results were evaluated using Böhler's angles, and calcaneal widths were determined using calcaneal axial and lateral radiographs obtained preoperatively and at last follow-up. RESULTS: Twenty (87%) of the 23 cases occurred in women, and the mean age of all patients was 65.8 years (43-90). The three men were older than 65. Five (21.7%) patients had osteopenia, and 12 (52.2%) had osteoporosis. Bone mineral density testing could not be performed in the other six patients. Clinical and radiographic results were significantly improved after surgery. CONCLUSION: Extra-articular calcaneal fractures of the joint depression type are much more common in women and occur at an older age than calcaneal fractures commonly occur. These fractures are also more common in patients with a low bone mineral density. LEVEL OF EVIDENCE: Level IV.

Lipid Emulsions Inhibit Labetalol-Induced Vasodilation in the Isolated Rat Aorta.

Lipid emulsions are used as adjuvant drugs to alleviate intractable cardiovascular collapse induced by drug toxicity. We aimed to examine the effect of lipid emulsions on labetalol-induced vasodilation and the underlying mechanism in the isolated rat aorta. We studied the effects of endothelial denudation, NW-nitro-l-arginine methyl ester (l-NAME), calmidazolium, methylene blue, 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one (ODQ), and lipid emulsions on labetalol-induced vasodilation. We also evaluated the effects of lipid emulsions on cyclic guanosine monophosphate (cGMP) formation, endothelial nitric oxide synthase (eNOS) phosphorylation, and endothelial calcium levels induced by labetalol. Labetalol-induced vasodilation was higher in endothelium-intact aortas than that in endothelium-denuded aortas. l-NAME, calmidazolium, methylene blue, and ODQ inhibited labetalol-induced vasodilation in endothelium-intact aortas. Lipid emulsions inhibited labetalol-induced vasodilation in endothelium-intact and endothelium-denuded aortas. l-NAME, ODQ, and lipid emulsions inhibited labetalol-induced cGMP formation in endothelium-intact aortas. Lipid emulsions reversed the stimulatory and inhibitory eNOS (Ser1177 and Thr495) phosphorylation induced by labetalol in human umbilical vein endothelial cells and inhibited the labetalol-induced endothelial calcium increase. Moreover, it decreased labetalol concentration. These results suggest that lipid emulsions inhibit vasodilation induced by toxic doses of labetalol, which is mediated by the inhibition of endothelial nitric oxide release and reduction of labetalol concentration.

Hypothermia Inhibits Dexmedetomidine-Induced Contractions in Isolated Rat Aortae.

Dexmedetomidine is widely used to induce sedation in the perioperative period. This study examined the effect of hypothermia (33 and 25 °C) on dexmedetomidine-induced contraction in an endothelium-intact aorta with or without the nitric oxide synthase inhibitor NW-nitro-L-arginine methyl ester (L-NAME). In addition, the effect of hypothermia on the contraction induced by dexmedetomidine in an endothelium-denuded aorta with or without a calcium-free Krebs solution was examined. The effects of hypothermia on the protein kinase C (PKC), myosin light chain (MLC20) phosphorylation, and Rho-kinase membrane translocation induced by dexmedetomidine were examined. Hypothermia inhibited dexmedetomidine-induced contraction in the endothelium-intact aorta with L-NAME or endothelium-denuded aorta. Hypothermia had almost no effect on the dexmedetomidine-induced contraction in the endothelium-denuded aorta with the calcium-free Krebs solution; however, the subsequent contraction induced by the addition of calcium was inhibited by hypothermia. Conversely, the transition from profound hypothermia back to normothermia reversed the hypothermia-induced inhibition of subsequent calcium-induced contractions. Hypothermia inhibited any contraction induced by KCl, PDBu, and NaF, as well as PKC and MLC20 phosphorylation and Rho-kinase membrane translocation induced by dexmedetomidine. These results suggest that hypothermia inhibits dexmedetomidine-induced contraction, which is mediated mainly by the impediment of calcium influx and partially by the attenuation of pathways involving PKC and Rho-kinase activation.

Induced membrane technique with plate fixation has a lower complication rate than bone transport over a plate for segmental tibial defects larger than 5 cm.

INTRODUCTION: The treatment of segmental tibial bone defects remains a surgical challenge. While Bone Transport (BT) and Induced Membrane Technique (IMT) are effective strategies for regenerating bone, there are few comparative studies between them. This investigation undertakes a comparative analysis of BT and IMT for large segmental tibial defects stabilised through plate fixation. MATERIALS AND METHODS: Patients with segmental tibial defects exceeding 5 cm were prospectively enrolled from 2008 to 2021 in a single institution, with a minimum follow-up duration of two years. All patients underwent either BT or IMT with plate fixation of the tibia. Procedural success, primary union as well as bone and functional outcome scores were compared. Complications, including non-unions, joint contractures and deep infections requiring surgical intervention, were also compared. RESULTS: 41 patients were recruited in total. 28 patients underwent Bone Transport Over a Plate (BTOP), while 13 patients underwent IMT with Plate fixation (IMTP). The procedural success rate trended higher in IMTP compared to BTOP (100% vs. 85.7%). The primary union rate also trended higher in IMTP compared to BTOP (92.3% vs. 79.2%). BTOP and IMTP achieved similar rates of satisfactory bone outcome scores (78.6% vs. 84.6%) and functional outcome scores (75% vs. 76.5%). There was no statistical difference between procedural success, primary union, bone and functional outcome scores. The complication rate in BTOP was 78.6% (22 of 28), including five docking site or regenerate non-unions, eight deep infections and nine joint contractures. IMTP had a 38.5% (5 of 13) complication rate, including one non-union, two deep infections and two joint contractures. The complication rate was 2.04 times higher in BTOP compared to IMTP (p = 0.0117). CONCLUSIONS: BTOP and IMTP are both equally effective techniques for regenerating bone in large tibial bone defects. However, IMTP may be a safer procedure than BTOP, with a lower probability of requiring additional procedures to address complications.

The orphan nuclear receptor SHP acts as a negative regulator in inflammatory signaling triggered by Toll-like receptors.

The orphan nuclear receptor SHP (small heterodimer partner) is a transcriptional corepressor that regulates hepatic metabolic pathways. Here we identified a role for SHP as an intrinsic negative regulator of Toll-like receptor (TLR)-triggered inflammatory responses. SHP-deficient mice were more susceptible to endotoxin-induced sepsis. SHP had dual regulatory functions in a canonical transcription factor NF-κB signaling pathway, acting as both a repressor of transactivation of the NF-κB subunit p65 and an inhibitor of polyubiquitination of the adaptor TRAF6. SHP-mediated inhibition of signaling via the TLR was mimicked by macrophage-stimulating protein (MSP), a strong inducer of SHP expression, via an AMP-activated protein kinase-dependent signaling pathway. Our data identify a previously unrecognized role for SHP in the regulation of TLR signaling.

Rubiarbonol B induces RIPK1-dependent necroptosis via NOX1-derived ROS production.

The activation of receptor-interacting protein kinase 1 (RIPK1) by death-inducing signaling complex (DISC) formation is essential for triggering the necroptotic mode of cell death under apoptosis-deficient conditions. Thus, targeting the induction of necroptosis by modulating RIPK1 activity could be an effective strategy to bypass apoptosis resistance in certain types of cancer. In this study, we screened a series of arborinane triterpenoids purified from Rubia philippinesis and identified rubiarbonol B (Ru-B) as a potent caspase-8 activator that induces DISC-mediated apoptosis in multiple types of cancer cells. However, in RIPK3-expressing human colorectal cancer (CRC) cells, the pharmacological or genetic inhibition of caspase-8 shifted the mode of cell death by Ru-B from apoptosis to necroptosis though upregulation of RIPK1 phosphorylation. Conversely, Ru-B-induced cell death was almost completely abrogated by RIPK1 deficiency. The enhanced RIPK1 phosphorylation and necroptosis triggered by Ru-B treatment occurred independently of tumor necrosis factor receptor signaling and was mediated by the production of reactive oxygen species via NADPH oxidase 1 in CRC cells. Thus, we propose Ru-B as a novel anticancer agent that activates RIPK1-dependent cell death via ROS production, and suggest its potential as a novel necroptosis-targeting compound in apoptosis-resistant CRC.

Trends in use of sodium-glucose co-transporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) in Australia in the era of increased evidence of their cardiovascular benefits (2014-2022).

PURPOSE: To investigate trends in SGLT2i and GLP-1RA use in Australia in the era of increased evidence of their cardiovascular benefits. METHODS: We used national dispensing claims for a 10% random sample of Australians to estimate the number of prevalent and new users (no dispensing in the prior year) of SGLT2i or GLP-1RA per month from January 2014 to July 2022. We assessed prescriber specialty and prior use of other antidiabetic and cardiovascular medicines as a proxy for evidence of type 2 diabetes (T2D) and cardiovascular conditions, respectively. RESULTS: We found a large increase in the number of prevalent users (216-fold for SGLT2i; 11-fold for GLP-1RA); in July 2022 approximately 250,000 Australians were dispensed SGLT2i and 120,000 GLP-1RA. Most new users of SGLT2i or GLP-1RA had evidence of both T2D and cardiovascular conditions, although from 2022 onwards, approximately one in five new users of SGLT2i did not have T2D. The proportion of new users initiating SGLT2i by cardiologists increased after 2021, reaching 10.0% of initiations in July 2022. Among new users with evidence of cardiovascular conditions, empagliflozin was the most commonly prescribed SGLT2i, while dulaglutide or semaglutide was the most common GLP-1RA. CONCLUSION: SGLT2i and GLP-1RA use is increasing in Australia, particularly in populations with higher cardiovascular risk. The increased use of SGLT2i among people without evidence of T2D suggests that best-evidence medicines are adopted in Australia across specialties, aligning with new evidence and expanding indications.

Theophylline-induced endothelium-dependent vasodilation is mediated by increased nitric oxide release and phosphodiesterase inhibition in rat aorta.

This study aimed to examine the endothelial dependence of vasodilation induced by the phosphodiesterase inhibitor theophylline in isolated rat thoracic aortas and elucidate the underlying mechanism, with emphasis on endothelial nitric oxide (NO). The effects of various inhibitors and endothelial denudation on theophylline-induced vasodilation, and the effect of theophylline on vasodilation induced by NO donor sodium nitroprusside, cyclic guanosine monophosphate (cGMP) analog bromo-cGMP, and ß-agonist isoproterenol in endothelium-denuded aorta were examined. The effects of theophylline and sodium nitroprusside on cGMP formation were also examined. We examined the effect of theophylline on endothelial nitric oxide synthase (eNOS) phosphorylation and intracellular calcium levels. Theophylline-induced vasodilation was greater in endothelium-intact aortas than that in endothelium-denuded aortas. The NOS inhibitor, NW-nitro-L-arginine methyl ester; non-specific guanylate cyclase (GC) inhibitor, methylene blue; and NO-sensitive GC inhibitor, 1H-[1,2,4]oxadiazolo[4,3-a] quinoxalin-1-one inhibited theophylline-induced vasodilation in endothelium-intact aortas. Theophylline increased the vasodilation induced by sodium nitroprusside, bromo-cGMP, and isoproterenol. Theophylline increased cGMP formation in endothelium-intact aortas, and sodium nitroprusside-induced cGMP formation in endothelium-denuded aortas. Moreover, theophylline increased stimulatory eNOS (Ser1177) phosphorylation and endothelial calcium levels, but decreased the phosphorylation of inhibitory eNOS (Thr495). These results suggested that theophylline-induced endothelium-dependent vasodilation was mediated by increased endothelial NO release and phosphodiesterase inhibition.

Correction: Chloroquine inhibits vasodilation induced by ATP-sensitive potassium channels in isolated rat aorta.

Another affiliation: 2 Department of Anesthesiology and Pain Medicine, Gyeongsang National University College of Medicine, Jinju-si, Gyeongsangnam-do, Republic of Korea was added for the author Kyeong-Eon Park at his own request.

Chloroquine inhibits vasodilation induced by ATP-sensitive potassium channels in isolated rat aorta.

This study examined the effect of chloroquine on vasodilation induced by levcromakalim in isolated endothelium-denuded rat aortas and clarified the underlying mechanisms. We examined the effects of chloroquine, hydroxychloroquine, lipid emulsion, reactive oxygen species (ROS) scavenger N-acetyl-ʟ-cysteine (NAC), and KATP channel inhibitor glibenclamide on levcromakaliminduced vasodilation. The effects of chloroquine, hydroxychloroquine, NAC, and levcromakalim on membrane hyperpolarization and ROS production were examined in aortic vascular smooth muscle cells (VSMCs). Chloroquine inhibited levcromakalim-induced vasodilation more than hydroxychloroquine. NAC attenuated chloroquine-mediated inhibition of levcromakalim-induced vasodilation, while lipid emulsion had no effect. Glibenclamide eliminated levcromakalim-induced vasodilation in aortas pretreated with chloroquine. Chloroquine and hydroxychloroquine inhibited levcromakalim-induced membrane hyperpolarization in VSMCs. Chloroquine and hydroxychloroquine both produced ROS, but chloroquine produced more. NAC inhibited chloroquine-induced ROS production in VSMCs. Collectively, these results suggest that, partially through ROS production, chloroquine inhibits levcromakalim-induced vasodilation. In addition, chloroquine-induced KATP channel-induced vasodilation impairment was not restored by lipid emulsion.

Superior capsular reconstruction using hybrid graft for irreparable massive rotator cuff tear.

PURPOSE: To evaluate the clinical and radiological outcomes of arthroscopic superior capsular reconstruction (SCR) using hybrid grafts composed of tensor fascia lata autografts and human dermal allografts. METHODS: This study included 30 patients with chronic irreparable posterosuperior rotator cuff tears (RCTs) who underwent arthroscopic SCR using a hybrid graft composed of tensor fascia lata autograft and human dermal allograft. Clinical outcomes were evaluated using the pain visual analogue scale score, shoulder range of motion, American Shoulder and Elbow Surgeons score, constant score, University of California-Los Angeles score, and simple shoulder test score preoperatively and at least 2 years after surgery. Radiographic analysis included the Hamada classification grade, acromiohumeral distance (AHD), and graft integrity at 2 years after surgery. RESULTS: All patients exhibited significant clinical improvement in all functional outcome measurements, except external rotation (all P < 0.05). The number of patients who exhibited pseudoparalysis decreased from 7 (23.3%) to 2 (6.7%) postoperatively. Complications were not observed. Radiologically, the mean postoperative AHD increased significantly from 6.9 ± 1.6 cm to 8.8 ± 2.1 cm at 2 years postoperatively (P < 0.001). Twenty five out of the 30 (83.3%) patients showed successful graft healing, and all healing failures occurred on the humeral side. The differences between the healed-graft and failed-graft groups were significantly lower graft thickness (P = 0.001) and smaller AHD (P < 0.001) in the failed-graft group. Every functional outcome scores were not statistically different between healed-graft and failed-graft groups. CONCLUSIONS: An arthroscopic SCR technique using a hybrid graft consisting of a tensor fascia lata autograft and human dermal allograft showed satisfactory clinical outcomes in patients with irreparable RCTs. LEVEL OF EVIDENCE: IV.

Lipid Emulsion Inhibits Amlodipine-Induced Nitric Oxide-Mediated Vasodilation in Isolated Rat Aorta.

This study aimed to examine the effect of lipid emulsion on the vasodilation induced by a toxic dose of amlodipine in isolated rat aorta and elucidate its mechanism, with a particular focus on nitric oxide. The effects of endothelial denudation, NW-nitro-L-arginvine methyl ester (L-NAME), methylene blue, lipid emulsion, and linolenic acid on the amlodipine-induced vasodilation and amlodipine-induced cyclic guanosine monophosphate (cGMP) production were examined. Furthermore, the effects of lipid emulsion, amlodipine, and PP2, either alone or combined, on endothelial nitric oxide synthase (eNOS), caveolin-1, and Src-kinase phosphorylation were examined. Amlodipine-induced vasodilation was higher in endothelium-intact aorta than in endothelium-denuded aorta. L-NAME, methylene blue, lipid emulsion, and linolenic acid inhibited amlodipine-induced vasodilation and amlodipine-induced cGMP production in the endothelium-intact aorta. Lipid emulsion reversed the increased stimulatory eNOS (Ser1177) phosphorylation and decreased inhibitory eNOS (Thr495) phosphorylation induced via amlodipine. PP2 inhibited stimulatory eNOS, caveolin-1, and Src-kinase phosphorylation induced via amlodipine. Lipid emulsion inhibited amlodipine-induced endothelial intracellular calcium increase. These results suggest that lipid emulsion attenuated the vasodilation induced via amlodipine through inhibiting nitric oxide release in isolated rat aorta, which seems to be mediated via reversal of stimulatory eNOS (Ser1177) phosphorylation and inhibitory eNOS (Thr495) dephosphorylation, which are also induced via amlodipine.

Transcriptome Profiling of Etridiazole-Exposed Zebrafish (Danio rerio) Embryos Reveals Pathways Associated with Cardiac and Ocular Toxicities.

Etridiazole (EDZ) is a thiadiazole-containing fungicide commonly used to control Pythium and Phytophthora spp. Although previous studies have shown that EDZ is teratogenic, the exact molecular mechanisms underlying its toxicity remain unknown. In this study, a zebrafish (Danio rerio; ZF) model was used to explore the molecular pathways associated with EDZ toxicity. The whole transcriptome of ZF embryos exposed to 96 h of EDZ was analyzed, along with developmental abnormalities. EDZ-induced malformations were primarily related to the eyes, heart, and growth of the ZF. Compared to untreated ZF, etridiazole-treated ZF had 2882 differentially expressed genes (DEGs), consisting of 1651 downregulated genes and 1231 upregulated genes. Gene ontology enrichment analysis showed that DEGs were involved in biological processes, such as sensory perception, visual perception, sensory organ development, and visual system development, and showed transmembrane transporter and peptidase regulator activities. Metabolism, phototransduction, aminoacyl-tRNA biosynthesis, MAPK signaling pathway, calcium signaling pathway, and vascular smooth muscle contraction were among the most enriched KEGG pathways. The qPCR analyses of the eight random genes were in good agreement with the transcriptome data. These results suggest several putative mechanisms underlying EDZ-induced developmental deformities in ZF.

The role of an augmentative plating in the management of femoral subtrochanteric nonunion.

INTRODUCTION: Owing to its distinct biomechanical properties, nonunion is common (7-20%) after intramedullary (IM) nailing of subtrochanteric femoral fractures. Unlike diaphyseal nonunion, it is difficult to provide sufficient stability by exchanging nailing alone in subtrochanteric nonunion. This study investigated the clinical outcomes of femoral subtrochanteric nonunion initially treated with an IM nail and subsequently managed with minimally invasive augmentative plate fixation. MATERIALS AND METHODS: Nineteen patients were enrolled retrospectively. The mechanisms of initial injury were traffic accidents in 8, falls from a height in seven, and slipping in two patients. Two patients with atypical subtrochanteric femoral fractures without a specific trauma history were further included. All patients underwent IM nailing as the index operation. Nonunion surgery was performed an average of 45.2 weeks after the initial surgery. In cases of hardware damage and/or atrophic nonunion, exchange nailing and bone grafting were performed in addition to augmentative plating, as necessary. Conversely, augmentative plating alone was performed in cases of hypertrophic nonunion without any failure of the preexisting IM nail or malalignment. A narrow locking compression plate was fixed after contouring according to the shape of the proximal femur. The mean follow-up period was 36.1 months. RESULTS: Bony union was achieved in 18/19 patients (94.7%), at an average of 19.8 weeks after nonunion surgery. In the case that did not heal even after exchange nailing, additional plating and bone grafting, further autogenous bone grafting was required after 11 months, which healed uneventfully. There were 2 cases of soft tissue irritation over the plate, but no major complications were observed. CONCLUSIONS: Additional plate augmentation over a retained IM nail yields satisfactory outcomes in terms of the bony union in subtrochanteric nonunion. Given its expected biomechanical superiority and relatively easy surgical technique, it may be a reasonable option for the management of femoral subtrochanteric nonunion.

Medication-related osteonecrosis of the jaw using periodontitis-induced rat before tooth extraction.

OBJECTIVE: This study aimed to investigate the occurrence of medication-related osteonecrosis of the jaw (MRONJ) after tooth extraction due to periodontitis in ovariectomized rats. METHODS: Twenty-four osteoporosis-induced rats were administered with zoledronic acid (ZA; ZA group) or saline (CONT group). In both groups, tooth extraction was performed after inducing periodontitis, and all animals were sacrificed 8-week after tooth extraction. RESULTS: Micro-CT of the tibia showed that the bone volume fraction, bone surface density, trabecular number, and bone mineral density were significantly higher in the ZA group than in the CONT group. Histologically, the proliferative zone on the growth plate was thicker in the ZA group than in the CONT group. Micro-CT of the extraction sites revealed that the bone volume fraction was significantly higher in the ZA group than in the CONT group. Radiologically, the ZA group showed partial healing and delayed healing. Histological analysis revealed normal bone healing status with completely healed epithelium in the extraction sites of the CONT group, whereas abnormal empty osteocytes in the necrotic bone and inflammatory infiltration were observed in the ZA group. CONCLUSION: The incidence of MRONJ increased in the rats administered with ZA.

Association between alcohol and bone mineral density in a Mendelian randomization study: the Dong-gu study.

INTRODUCTION: Many previous studies have reported a positive relationship between alcohol and bone mineral density (BMD). However, the causality between alcohol and BMD has not been fully evaluated. MATERIALS AND METHODS: This study enrolled 8892 participants from the Dong-gu study. Mendelian randomization (MR) using two-stage least-squared regression was used to evaluate the association between the genetically predicted amount of alcohol consumption per day and BMD. The aldehyde dehydrogenase 2 (ALDH2) rs671 polymorphism was used as instrumental variables for alcohol consumption. Age, smoking history, and BMI were adjusted in the multivariate model. RESULTS: Self-reported alcohol consumption was positively related to total hip and lumbar spine BMD in both sexes. In multivariate Mendelian randomization analysis, the genetically predicted amount of alcohol consumption was positively associated with both total hip and lumbar spine BMD in men. Total hip BMD and lumbar spine BMD increased by 0.004 g/cm2 (95% confidence interval [CI] 0.002-0.007) and 0.007 g/cm2 (95% CI 0.004-0.011) with doubling of alcohol consumption. However, in women, genetically predicted alcohol consumption was not significantly associated with BMD. CONCLUSION: In our MR study, genetically predicted alcohol consumption was positively associated with BMD in men. This result suggests that the association between alcohol consumption and BMD is causal.

Carcinoma ex pleomorphic adenoma of the parotid gland.

INTRODUCTION: Carcinoma ex pleomorphic adenoma (CXPA) is a rare malignant tumor of the parotid gland. We analyzed the clinical characteristics and treatment outcomes of CXPA of the parotid gland in patients managed for 11 years at this hospital. METHODS: The study included 17 cases of CXPA of the parotid gland from January 2010 to December 2020. RESULTS: Over 11 years, CXPA was the fourth most common parotid carcinoma, accounting for 9.4% of the 180 cases finally diagnosed as parotid carcinoma. Of the 17 cases of CXPA of the parotid gland, 12 lesions were removed by superficial parotidectomy, four lesions by total parotidectomy, and one lesion by radical parotidectomy. Four patients underwent neck dissection. The most common histopathology type was salivary duct carcinoma (n = 13, 76.5%). Postoperative radiation therapy (RT) was performed in 15 patients. Two patients (11.8%) experienced CXPA recurrence 14 and 19 months after surgery. CONCLUSION: CXPA of the parotid gland was treated without recurrence in about 90% of the patients through surgery and postoperative RT. In the case of frankly invasive or adverse factors in the histopathological examination, more attention is required because CXPA recurrence may occur more frequently.

Mid-term to Long-term Follow-up Results of Reconstruction for Thumb Radial Polydactyly.

BACKGROUND: Preaxial or radial polydactyly is one of the most common hand congenital anomalies in newborns. Contemporary reconstruction methods include ligament reconstruction, excision of the polydactylous thumb, osteotomy, and other surgical techniques according to the type of polydactyly. The purpose of this study was to report mid-term to long-term reconstruction results for thumb (radial) polydactyly. METHODS: We retrospectively reviewed the medical records of patients who underwent reconstruction surgery for preaxial polydactyly. Clinical outcomes, including the range of motion (ROM), pain, and complications, were evaluated. We assessed the final radiographs of the reconstructed thumb to identify the potential development of arthritis or other remaining deformities. After excluding cases without a simple radiograph and cases with a short follow-up period of fewer than 5 years, 26 thumbs were included. The surgical technique followed including excision of polydactylout thumb was tailored to the type of polydactyly. If the nail size of the thumbs was similar, the Bilhaut-Cloquet method was preferred. RESULTS: The mean age of the patients at the surgery and final follow-up was 14.9 months (range: 8 to 30 mo) and 11.9 years (range: 5.8 to 19.3 y), respectively. The mean follow-up was 128.8 months years (range: 60 to 219 mo), and the mean ROM of the thumb was 32.7 and 57.5 degrees in the distal interphalangeal joint (DIP) and metacarpophalangeal (MP) joint, respectively. Ulnar or radial side instability was prominent in 7 patients in the involved joints (26.9%). One patient underwent interphalangeal (IP) fusion for extension lag with pain. The radiologic evaluation revealed that 2 patients developed radiographic evidence of IP joint arthritis (7.7%). Radial deviation of the MP or IP joint existed in 13 cases (range: 5 to 40 degrees) (50.0%), and ulnar deviation of the MP or IP joint existed in 2 cases (range: 19 to 20 degrees) (7.7%). CONCLUSIONS: In mid-term to long-term experience, sequelae such as joint instability, joint stiffness, and remaining deformity cannot be neglected. An unstable MP joint may result if the DIP joint remains stiff or has a lower ROM. LEVEL OF EVIDENCE: Level IV-therapeutic studies.

Peri-implant atypical femoral fracture after nail or plate osteosynthesis.

BACKGROUND: A lack of scientific information regarding the risk factors and diagnosis of peri-implant atypical femoral fracture (PI-AFF) exists. We report a case series of developed PI-AFF with a nail or plate construct wherein prior femoral fractures were already healed after osteosynthesis. This study aimed to identify the cause and risk factors of PI-AFF and to devise a preventive method based on this. METHODS: We identified 11 PI-AFFs displaying features of AFFs. All patients were ambulant females (mean age, 74.9 years). The mean T-score of the femur measured by DEXA (Dual Energy X-ray Absorptiometry) scan was 3.5. Osteosynthesis was performed with a plate and an intramedullary nail in six and five patients, respectively. Possible risk factors were investigated, including the used implant, the medication of bisphosphonate, the characteristics of previous fracture (AFF or non-AFF), and the co-existence of AFF on the contralateral side. RESULTS: The PI-AFFs developed at an average of 6.6 years from the time of prior fracture. All fractures were located at the screw through the plate or nail. Regarding anatomic locations, seven and four fractures were at the subtrochanteric area and diaphysis, respectively. Diaphyseal PI-AFFs occurred in plating cases, all of which were associated with excessive femoral bowing. Subtrochanteric PI-AFFs included all five patients with nail fixation, which occurred near a proximal interlocking screw. Six of the 11 patients were on bisphosphonate treatment before or at the time of fracture. The duration of bisphosphonate treatment was 6 years on average. Concerning the previous femoral fractures, seven and four patients were AFF and non-AFF, respectively. Considering the pathology on the contralateral leg, eight had suffered diaphyseal AFF. Four patients were treated nonoperatively. Seven patients needed an operation; 6 of them healed after reconstruction nailing, and one needed hip arthroplasty because of the associated displaced femoral neck fracture. CONCLUSIONS: PI-AFFs may develop through the screw hole at the subtrochanteric or diaphyseal area due to femoral fragility and stress riser effect of the implant. An improved osteosynthesis strategy may be necessary to avoid PI-AFFs when fixing osteoporotic femoral fractures.