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The Bone & Joint Journal Jul 2024Proximal humeral fractures are the third most common fracture among the elderly. Complications associated with fixation include screw perforation, varus collapse, and... (Meta-Analysis)
Meta-Analysis Comparative Study
AIMS
Proximal humeral fractures are the third most common fracture among the elderly. Complications associated with fixation include screw perforation, varus collapse, and avascular necrosis of the humeral head. To address these challenges, various augmentation techniques to increase medial column support have been developed. There are currently no recent studies that definitively establish the superiority of augmented fixation over non-augmented implants in the surgical treatment of proximal humeral fractures. The aim of this systematic review and meta-analysis was to compare the outcomes of patients who underwent locking-plate fixation with cement augmentation or bone-graft augmentation versus those who underwent locking-plate fixation without augmentation for proximal humeral fractures.
METHODS
The search was carried out according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Articles involving patients with complex proximal humeral fractures treated using open reduction with locking-plate fixation, with or without augmentation, were considered. A meta-analysis of comparative studies comparing locking-plate fixation with cement augmentation or with bone-graft augmentation versus locking-plate fixation without augmentation was performed.
RESULTS
A total of 19 studies were included in the qualitative synthesis, and six comparative studies were included in the meta-analysis. Overall, 120 patients received locking-plate fixation with bone-graft augmentation, 179 patients received locking-plate fixation with cement augmentation, and 336 patients received locking-plate fixation without augmentation. No statistically relevant differences between the augmented and non-augmented cohorts were found in terms of the Disabilities of the Arm, Shoulder and Hand questionnaire score and Constant-Murley Score. The cement-augmented group had a significantly lower rate of complications compared to the non-augmented group.
CONCLUSION
While locking-plate fixation with cement augmentation appears to produce a lower complication rate compared to locking-plate fixation alone, functional outcomes seem comparable between augmented and non-augmented techniques.
Topics: Humans; Bone Plates; Shoulder Fractures; Fracture Fixation, Internal; Bone Cements; Bone Transplantation; Treatment Outcome
PubMed: 38945543
DOI: 10.1302/0301-620X.106B7.BJJ-2023-1113.R1 -
Revista Portuguesa de Cardiologia :... Jun 2024Chronic thromboembolic pulmonary hypertension (CTEPH) is part of group 4 of the pulmonary hypertension (PH) classification and generally affects more than a third of... (Review)
Review
Chronic thromboembolic pulmonary hypertension (CTEPH) is part of group 4 of the pulmonary hypertension (PH) classification and generally affects more than a third of patients referred to PH centers. It is a three-compartment disease involving proximal (lobar-to-segmental) and distal (subsegmental) pulmonary arteries that are obstructed by persistent fibrothrombotic material, and precapillary pulmonary arteries that can be affected as in pulmonary arterial hypertension. It is a rare complication of pulmonary embolism (PE), with an incidence of around 3% in PE survivors. The observed incidence of CTEPH in the general population is around six cases per million but could be three times higher than this, as estimated from PE incidence. However, a previous venous thromboembolic episode is not always documented. With advances in multimodality imaging and therapeutic management, survival for CTEPH has improved for both operable and inoperable patients. Advanced imaging with pulmonary angiography helps distinguish proximal from distal obstructive disease. However, right heart catheterization is of utmost importance to establish the diagnosis and hemodynamic severity of PH. The therapeutic strategy relies on a stepwise approach, starting with an operability assessment. Pulmonary endarterectomy (PEA), also known as pulmonary thromboendarterectomy, is the first-line treatment for operable patients. Growing experience and advances in surgical technique have enabled expansion of the distal limits of PEA and significant improvements in perioperative and mid- to long-term mortality. In patients who are inoperable or who have persistent/recurrent PH after PEA, medical therapy and/or balloon pulmonary angioplasty (BPA) are effective treatment options with favorable outcomes that are increasingly used. All treatment decisions should be made with a multidisciplinary team that includes a PEA surgeon, a BPA expert, and a chest radiologist.
PubMed: 38945473
DOI: 10.1016/j.repc.2024.04.006 -
The Journal of Biological Chemistry Jun 2024Mammalian RNA polymerase II preinitiation complexes assemble adjacent to a nucleosome whose proximal edge (NPE) is typically 40-50 bp downstream of the transcription...
Mammalian RNA polymerase II preinitiation complexes assemble adjacent to a nucleosome whose proximal edge (NPE) is typically 40-50 bp downstream of the transcription start site (TSS). At active promoters, that +1 nucleosome is universally modified by trimethylation on lysine 4 of histone H3 (H3K4me3). The Pol II preinitiation complex only extends 35 bp beyond the TSS, but nucleosomal templates with an NPE at +51 are nearly inactive in vitro with promoters that lack a TATA element and thus depend on TFIID for promoter recognition. Significantly, this inhibition is relieved when the +1 nucleosome contains H3K4me3, which can interact with TFIID subunits. Here we show that H3K4me3 templates with both TATA and TATA-less promoters are active with +35 NPEs when transcription is driven by TFIID. Templates with +20 NPE are also active but at reduced levels compared to +35 and +51 NPEs, consistent with a general inhibition of promoter function when the proximal nucleosome encroaches on the preinitation complex. Remarkably, dinucleosome templates support transcription when H3K4me3 is only present in the distal nucleosome, suggesting that TFIID-H3K4me3 interaction does not require modification of the +1 nucleosome. Transcription reactions performed with an alternative protocol that retains most nuclear factors results primarily in early termination, with a minority of complexes successfully traversing the first nucleosome. In such reactions the +1 nucleosome does not substantially affect the level of termination even with an NPE of +20, indicating that a nucleosome barrier is not a major driver of early termination by Pol II.
PubMed: 38945447
DOI: 10.1016/j.jbc.2024.107515 -
Toxicology Jun 2024Ochratoxin A (OTA) is a rat renal carcinogen that induces karyomegaly and micronuclei in proximal tubular epithelial cells (PTECs). We previously performed comprehensive...
Involvement of multiple epigenetic mechanisms by altered DNA methylation from the early stage of renal carcinogenesis before proliferative lesion formation upon repeated administration of ochratoxin A.
Ochratoxin A (OTA) is a rat renal carcinogen that induces karyomegaly and micronuclei in proximal tubular epithelial cells (PTECs). We previously performed comprehensive gene profiling of alterations in promoter-region methylation and gene expression in PTECs of rats treated with OTA for 13 weeks. The OTA-specific gene profile was obtained by excluding genes showing expression changes similar to those upon treatment with 3-chloro-1,2-propanediol, a renal carcinogen not inducing karyomegaly. In this study, we validated the candidate genes using methylated DNA enrichment PCR and real-time RT-PCR, and identified Gen1, Anxa3, Cdkn1a, and Osm as genes showing OTA-specific epigenetic changes. These genes and related molecules were subjected to gene expression and immunohistochemical analyses in the PTECs of rats treated with OTA, other renal carcinogens, or non-carcinogenic renal toxicants for 4 or 13 weeks. Cdkn1a upregulation and increase of p21 karyomegalic PTECs were observed with OTA, matching the findings associated with micronucleus-inducing carcinogens. This suggested that the increase of p21 karyomegalic PTECs is linked to micronucleus formation, which in turn accelerates chromosomal instability. The upregulation of Cdkn1a-related genes with OTA suggests the acquisition of a senescence-associated secretory phenotype, which promotes the establishment of a carcinogenic environment. Meanwhile, OTA specifically caused a decrease of GEN1 PTECs reflecting Gen1 downregulation and an increase of ANXA3 PTECs reflecting Anxa3 upregulation, as well as Osm upregulation. OTA may efficiently disrupt pathways for repairing the DNA double-strand breaks that it itself causes, via Gen1 downregulation, and enhance cell proliferation through the upregulation of Anxa3 and Osm. This may exacerbate the chromosomal instability from the early stage of OTA-induced renal carcinogenesis before proliferative lesions form. OTA may cause renal carcinogenesis involving multiple epigenetic mechanisms.
PubMed: 38945198
DOI: 10.1016/j.tox.2024.153875 -
International Journal of Surgery Case... Jun 2024Myeloid sarcoma (MS) is a rare extramedullary tumor composed of malignant myeloid cells that most commonly arise in patients previously diagnosed with myeloproliferative...
INTRODUCTION
Myeloid sarcoma (MS) is a rare extramedullary tumor composed of malignant myeloid cells that most commonly arise in patients previously diagnosed with myeloproliferative disease. However, they can still occur in isolation and without bone marrow disease.
CASE PRESENTATION
An 8-year-old girl who had a history of acute myeloid leukemia and was off treatment for four years presented to the clinic with a history of on and off left knee swelling and pain without any direct trauma to the knee over the last two years. Knee Magnetic resonance imaging (MRI) showed diffused joint effusion with proximal tibia focal edema. A diagnosis of juvenile rheumatoid arthritis was suspected, and the patient was started on treatment, but the problem did not resolve. Eventually, the patient underwent a repeat MRI and showed increased joint effusion with an increase in the focal edema. An open bone biopsy of the lesion was taken, and the histopathology showed sheets of primitive mononuclear cells positive for CD33 and CD117 and negative for CD34, myeloperoxidase, CD10, CD20, and CD68, indicating myeloid sarcoma.
CLINICAL DISCUSSION
Histological examination and immunohistochemistry are the most important in diagnosing myeloid sarcoma. Previously, before the introduction of chemotherapy and stem cell transplant, such cases of proximal tibia MS were treated with surgical resection of the bone. However, chemotherapy with the possibility of an allogeneic hematopoietic stem cell transplant (alloHSCT) has changed the view of survival in such cases.
CONCLUSION
Isolated proximal tibia myeloid sarcoma is a rare occurrence that can be misdiagnosed and lead to delayed treatment. Bone biopsy, Immunohistochemistry, and cytogenetic studies play a critical role in differentiating MS from other types of tumors.
PubMed: 38945014
DOI: 10.1016/j.ijscr.2024.109956 -
Chembiochem : a European Journal of... Jun 2024Antibody-enzyme conjugates have shown potential as tissue-specific prodrug activators by antibody-directed enzyme prodrug therapy (ADEPT), but the approach met...
Antibody-enzyme conjugates have shown potential as tissue-specific prodrug activators by antibody-directed enzyme prodrug therapy (ADEPT), but the approach met challenges clinically due to systemic drug release. Here, we report a novel dual-targeting ADEPT system (DuADEPT) which is based on active cancer receptor targeting of both a trastuzumab-sialidase conjugate (Tz-Sia) and a highly potent sialidase-activated monomethyl auristatin E (MMAE) prodrug scaffold. The scaffold is based on a four-way junction of the artificial nucleic acid analog acyclic (L)-threoninol nucleic acid ((L)-aTNA) which at the ends of its four arms carries one nanobody targeting HER2 and three copies of the prodrug. Dual-targeting of the constructs to two proximal epitopes of HER2 was shown by flow cytometry, and a dual-targeted enzymatic drug release assay revealed cytotoxicity upon prodrug activation specifically for HER2-positive cancer cells. The specific delivery and activation of prodrugs in this way could potentially be used to decrease systemic side effects and increase drug efficacy, and utilization of Tz-Sia provides an opportunity to combine the local chemotherapeutic effect of the DuADEPT with an anticancer immune response.
PubMed: 38945824
DOI: 10.1002/cbic.202400437 -
Mymensingh Medical Journal : MMJ Jul 2024Soft tissue injuries of the hand or forearm often results in exposure of tendon or bone which needs coverage with a suitable flap. This prospective observational study... (Observational Study)
Observational Study
Soft tissue injuries of the hand or forearm often results in exposure of tendon or bone which needs coverage with a suitable flap. This prospective observational study was carried out in National Institute of Traumatology and Orthopaedic Rehabilitation (NITOR), Dhaka, Bangladesh from February 2019 to January 2020, to evaluate the use of the pedicled paraumbilical perforator flaps as a reliable flap to cover such defects. Total 34 patients having soft tissue defects in the hand and forearm with exposed tendons, bones or implant were included in this study. All the defects were covered by paraumbilical perforator flap. The defects were caused by road traffic accident (n=22), machinery injury (n=10) and burn injury (n=2). Sixteen patients had defects involving the forearm, six over dorsum of hand, another two over first web space and the rest had defects over two or more areas of forearm, hand and wrist. Lateral extent of flaps was upto anterior axillary line in 41.18% cases and upto mid-axillary line in 55.88% cases. Flap division and final inset was done in second stage after 3 weeks. Donor site closed primarily in all cases, except in two cases where it was covered by skin graft. All the flaps survived with no incidence of flap necrosis, dehiscence or infection after first stage. However, after the division of the flap, two patients developed marginal necrosis of the proximal margin which healed spontaneously by conservative treatment. The mean flap surface area utilized was 108 cm2. Donor area healed well without any major complications. Three patients developing scar hypertrophy were treated with intra-lesional triamcinolone injections. The paraumbilical perforator flap is a reliable option to cover soft tissue defects of hand and forearm due to easier planning and harvesting of the flap, adequate skin paddle and minimum donor site morbidity.
Topics: Humans; Perforator Flap; Male; Soft Tissue Injuries; Female; Adult; Prospective Studies; Hand Injuries; Middle Aged; Forearm; Adolescent; Forearm Injuries; Young Adult; Plastic Surgery Procedures; Child
PubMed: 38944720
DOI: No ID Found -
Mymensingh Medical Journal : MMJ Jul 2024The bicipital groove is a groove on the anterior aspect of the proximal end of the humerus. It lies between the greater and lesser tubercles. The variations of this...
The bicipital groove is a groove on the anterior aspect of the proximal end of the humerus. It lies between the greater and lesser tubercles. The variations of this groove may lead to various pathologies of the biceps brachii tendon, one of the most common causes of shoulder pain. Hence, this study examines the various osteometric parameters of bicipital groove in the Bangladeshi population. This cross-sectional descriptive study was done on 100 dry adult human cadaveric humeri (43 right sides and 57 left sides) in the Department of Anatomy, Mymensingh Medical College, Bangladesh from July 2021 to June 2022. The length, maximum width and depth of the bicipital groove and the length of this groove's medial and lateral walls were measured using a digital Vernier slide caliper. Data were recorded in a predesigned data sheet separately and analyzed statistically using Microsoft Excel and SPSS. According to the present study, the mean±SD length of the bicipital groove of the right humeri was 66.646±11.563mm and the left humeri were 66.002±13.025mm. The mean±SD maximum width of the bicipital groove of the right humeri was 10.870±1.799mm and the left humeri were 11.480±1.402mm. The mean±SD depth of the bicipital groove of the right humeri was 4.242±0.655mm and the left humeri were 4.452±0.854mm. The mean±SD medial wall length of the bicipital groove of the right humeri was 60.671±12.360mm and the left humeri were 59.161±13.660mm. The mean±SD lateral wall length of the bicipital groove of the right-sided humeri was 64.996±11.611mm and the left humeri were 64.074±13.115mm. It is expected that this osteometric study of bicipital groove among the Bangladeshi population will be very helpful for clinical anatomists, orthopaedic surgeons, anthropologists and radiologists.
Topics: Humans; Bangladesh; Cross-Sectional Studies; Cadaver; Humerus; Adult; Male; Female
PubMed: 38944704
DOI: No ID Found -
Cardiovascular and Interventional... Jun 2024Retrograde type A aortic dissection (RTAD) represents a serious complication of endovascular treatment for type B aortic dissection (TBAD). To avoid RTAD, it is...
PURPOSE
Retrograde type A aortic dissection (RTAD) represents a serious complication of endovascular treatment for type B aortic dissection (TBAD). To avoid RTAD, it is recommended to land the proximal end of the stent graft in a non-dissected aortic segment. In this study, we investigated whether landing in the dissection area increased the number of events at the proximal site.
METHODS
We conducted a retrospective review of endovascular treatments for TBAD at a single institution between 2009 and 2022. Patients were divided into two groups: group A, with a proximal landing zone entirely within the dissected area, and group B, with the proximal extent of the seal zone in the non-dissected area. We evaluated the occurrence of proximal events, including RTAD, and examined long-term outcomes to assess the validity of landing in the dissection area.
RESULTS
The study included eighty-nine patients who underwent endovascular treatment for TBAD. New intimal tears in the proximal landing site occurred in 3 cases (3.4%), with 1 case (2%) in group A and 2 cases (5.1%) in group B, showing no significant difference. Among the three cases, one (1.1%) in group B with zone 2 landing resulted in RTAD. At 60 months, the overall survival was 85%, and freedom from aorta-related mortality was 88%, with no significant difference between the groups.
CONCLUSION
Even if the proximal landing is in a dissected area, a treatment strategy performed in zone 3 without proximal landing in zone 2, seeking a non-dissected area, can still provide sufficient therapeutic effects. Level of Evidence 3 Retrospective single-center cohort analysis.
PubMed: 38944660
DOI: 10.1007/s00270-024-03791-0 -
Journal of Pediatric Urology Jun 2024The bladder exstrophy-epispadias complex includes some of the most challenging conditions treated by pediatric urologists. They are associated with the need for multiple...
Redo surgery to improve urinary function, sexual function and cosmesis in male patients with exstrophy-epispadias complex complications. Technical principles and pearls based on case scenarios.
The bladder exstrophy-epispadias complex includes some of the most challenging conditions treated by pediatric urologists. They are associated with the need for multiple intricate reconstructive procedures, aimed at restoring the anatomy and function of the bladder, urethra and external genitalia. These patients often endure multiple redo reconstructive procedures to improve urinary function, sexual function and cosmesis throughout the first two decades of life. In this article, we present the 30-year experience of a single surgeon performing redo surgery for males born with epispadias and bladder exstrophy. Through detailed documentation of 6 clinical cases, we highlight technical aspects that may contribute to a successful surgical reconstruction in these patients. The article is focused specifically on patients undergoing redo epispadias repair with or without concomitant continence procedures. We make the case for complete penile disassembly with external rotation of the corpora to correct recurrent dorsal curvature; this approach also allows the surgeon to have access to the proximal urethra and bladder neck after opening the intersymphiseal scar/band. This is useful when additional procedures on the bladder, such as bladder neck tailoring, are necessary. We also highlight the importance of avoiding reverse Byars' flaps when performing skin closure, due to the resulting midline scar. Besides being associated with a poor cosmetic outcome, it can also contribute to recurrent dorsal curvature. The authors advocate for rotational skin flaps to cover the penile shaft. Correction of dorsal curvature and improved cosmesis obtained with complete penile disassembly sometimes comes at the expense of the urethra being left as a hypospadias (figure). This will require further surgeries (usually a 2-stage buccal mucosa graft), much like the treatment of proximal hypospadias. Redo epispadias surgery in males remains a challenge. The systematic approach offered by the case scenarios may help guide surgeons dealing with this difficult condition. Patient with complications after repair of classic bladder exstrophy. A) Stone retrieved from posterior urethra after complete penile disassembly. B) After opening the inter-symphiseal scar, the bladder has been opened and the bladder neck tailored. C) Complete penile disassembly has been completed with corporal bodies and urethra individualized. D,E,F) Final appearance of the repair; abdominal wall was closed with anterior rectus sheath flaps, penile skin was closed with rotational flaps and urethra ended up as a hypospadias.
PubMed: 38944626
DOI: 10.1016/j.jpurol.2024.06.004