Exploring the Implications of Golgi Apparatus Dysfunction in Bone Diseases.

The Golgi apparatus is an organelle responsible for protein processing, sorting, and transport in cells. Recent research has shed light on its possible role in the pathogenesis of various bone diseases. This review seeks to explore its significance in osteoporosis, osteogenesis imperfecta, and other bone conditions such as dysplasias. Numerous lines of evidence demonstrate that perturbations to Golgi apparatus function can disrupt post-translational protein modification, folding and trafficking functions crucial for bone formation, mineralization, and remodeling. Abnormalities related to glycosylation, protein sorting, or vesicular transport in Golgi have been associated with altered osteoblast and osteoclast function, compromised extracellular matrix composition, as well as disrupted signaling pathways involved with homeostasis of bones. Mutations or dysregulation of Golgi-associated proteins, including golgins and coat protein complex I and coat protein complex II coat components, have also been implicated in bone diseases. Such genetic alterations may disrupt Golgi structure, membrane dynamics, and protein transport, leading to bone phenotype abnormalities. Understanding the links between Golgi apparatus dysfunction and bone diseases could provide novel insights into disease pathogenesis and potential therapeutic targets. Future research should focus on unraveling specific molecular mechanisms underlying Golgi dysfunction associated with bone diseases to develop targeted interventions for restoring normal bone homeostasis while decreasing clinical manifestations associated with these issues.

The Use and Potential Benefits of N-Acetylcysteine in Non-Acetaminophen Acute Liver Failure: An Etiology-Based Review.

Acute liver failure represents a life-threatening organ dysfunction with high mortality rates and an urgent need for liver transplantation. The etiology of the disease varies widely depending on various socio-economic factors and is represented mainly by paracetamol overdose and other drug-induced forms of liver dysfunction in the developed world and by viral hepatitis and mushroom poisoning in less developed countries. Current medical care constitutes either specific antidotes or supportive measures to ensure spontaneous recovery. Although it has been proven to have beneficial effects in paracetamol-induced liver failure, N-acetylcysteine is widely used for all forms of acute liver failure. Despite this, few well-designed studies have been conducted on the assessment of the potential benefits, dose regimens, or route of administration of N-acetylcysteine in non-acetaminophen liver failure. This review aims to summarize the current evidence behind the use of this drug in different forms of liver failure.

The Role of Fascial Tissue Layer in Electric Signal Transmission from the Forearm Musculature to the Cutaneous Layer as a Possibility for Increased Signal Strength in Myoelectric Forearm Exoprosthesis Development.

Myoelectric exoprostheses serve to aid in the everyday activities of patients with forearm or hand amputations. While electrical signals are known key factors controlling exoprosthesis, little is known about how we can improve their transmission strength from the forearm muscles as to obtain better sEMG. The purpose of this study is to evaluate the role of the forearm fascial layer in transmitting myoelectrical current. We examined the sEMG signals in three individual muscles, each from six healthy forearms (Group 1) and six amputation stumps (Group 2), along with their complete biometric characteristics. Following the tests, one patient underwent a circumferential osteoneuromuscular stump revision surgery (CONM) that also involved partial removal of fascia and subcutaneous fat in the amputation stump, with re-testing after complete healing. In group 1, we obtained a stronger sEMG signal than in Group 2. In the CONM case, after surgery, the patient's data suggest that the removal of fascia, alongside the fibrotic and subcutaneous fat tissue, generates a stronger sEMG signal. Therefore, a reduction in the fascial layer, especially if accompanied by a reduction of the subcutaneous fat layer may prove significant for improving the strength of sEMG signals used in the control of modern exoprosthetics.

Patellar Resurfacing in Total Knee Arthroplasty, a Never-Ending Controversy; Case Report and Literature Review.

Total knee arthroplasty (TKA) remains a lifesaving procedure for advanced gonarthrosis. However, patella resurfacing (PR) in TKA remains a controversial procedure, leading to extensive discussions amongst orthopedic surgeons, regarding its indications and results. Based on these premises, we present a clinical case of a 70-year-old Caucasian woman admitted for pain, swelling and limitation of left knee joint mobility. Her medical history records an Ahlback stage IV gonarthrosis with simultaneous bilateral TKA surgery performed in different hospital, when two NexGen cemented total prostheses were implanted with patellar resurfacing being performed only on the right side. Our clinical (American Knee Society Score, Lonner and Feller scales) and radiological evaluations (CT scan and Xray) revealed left patellar arthrosis and a slight lateral subluxation of the patella. The chosen treatment plan was revision surgery for PR and patellar prosthesis with a cemented patellar component, cross-linked polyethylene, no 32 NexGen model with 8.5 mm thickness. The immediate and distant postoperative evolution was favorable. Extensive literature review shows that, at present, PR remains at surgeon's discretion mainly based on his previous results. Therefore, we believe there is an imperative need to develop high quality studies based on accurate scientific evidence to universally establish valid guidelines for PR in TKA.

Autoimmune encephalitis and paraneoplastic encephalitis: difficulties in diagnosis and management in the ICU.

Autoimmune encephalitis (AIE) represents a category of relatively newly described neurological disorders associated with an increasing prevalence, a significant impact on the healthcare system, and a high rate of intensive care unit (ICU) admission. This category of diseases often requires prompt treatment, even before a definitive diagnosis is established. In the ICU, patients present with nonspecific signs and symptoms for AIE, which pose challenges in both management and diagnosis. Patients frequently exhibit dysautonomia, severe physical and psychic agitation, as well as tremors and dyskinesia, all of which complicate the diagnosis. They are prone to developing infections, including ventilator-associated pneumonia, and issues related to difficult venous access and pressure ulcers. Early initiation of immunosuppressive treatment is necessary to improve patients' outcome. Through this article, we aimed to summarize current knowledge in terms of the difficulties in diagnosing and management of this pathology in the ICU, as well as the implications for the healthcare system in terms of human and financial resources.

In Vivo Study of Local and Systemic Responses to Clinical Use of Mg-1Ca Bioresorbable Orthopedic Implants.

(1) Background: Resorbable Mg-based implants represent a new direction in orthopedic surgery but have some drawbacks, such as their rapid biodegradation and increased rate of corrosion. Some in vitro studies hypothesized that tissue necrosis, incision dehiscence, risk of gas embolization in vital organs, interference with coagulation processes, and trophocyte viability impairment can occur. (2) Methods: We conducted an in vivo study on ten rabbit cases, in two groups; group one, consisting of six cases, received cylindrical implants of Mg-1Ca alloy in tibial intramedullary bone tissue. Group two, consisting of four cases, received Mg-1Ca parallelepiped implants, in the thigh muscular tissue. We recorded and compared weight (preoperatively and at 2, 4, and 6 weeks postoperatively), complete blood count, serum electrolytes, liver and kidney functional markers, and coagulation parameters, prior to and at 6 weeks after surgery. Local evolution was assessed radiologically and with tissue biopsies with complete pathology analysis. (3) Results: All biological markers and clinical evolution were favorable, showing good integration of the implants with none of the local or systemic signs of degradation. (4) Conclusions: Our study shows that the clinical use of Mg-1Ca bioresorbable alloys can be safe as none of the cited local or systemic complications have been identified.

Primary Bone Lesions in Rosai-Dorfman Disease, a Rare Case and Diagnostic Challenge-Case Report and Literature Review.

Rosai-Dorfman Disease (RDD), also known as sinus histiocytosis, is included in the group of rare diseases, characterized by proliferation and accumulation of histiocytes in the lymph nodes (lymphadenopathy), most often involving the cervical ganglion chains (nodal form). RDD bone involvement is rare, estimated at 10% of cases, but primary bone involvement (extranodal form), is very rare-2-8%. Usually they are solitary lesions, with multifocal primary bone manifestations being extremely rare. Histopathological analysis is of high value for a correct diagnosis. We present the case of a Caucasian woman, 42 years old, initially treated in another clinic, for an osteolytic tumor formation in the right tibial shaft. An excisional biopsy with bone trepanation was performed, the histopathological diagnosis being the chronic inflammatory tissue. The evolution was atypical, with tumor growth, extraosseous, subcutaneous. A needle biopsy was repeated in our clinic, the result being similar to the original one. Evolution of the tumor, and the radiological and imaging aspect (periosteal reaction, eroded and thin bone cortex) suggested a more aggressive disease, these being in inconsistency with the result obtained. The biopsy was repeated, as an excision type this time. The histopathological result and immunohistochemistry indicated an RDD primary bone lesion. Based on this result, and corroborated with the data from the literature, we initiated the surgical treatment, curettage and grafting with bone substitute plus safety osteosynthesis with locked plaque, the patient registering a favorable evolution. RDD primary bone lesions are in fact an atypical manifestation of a rare disease. The correct diagnosis is very difficult due to the non-specific imaging aspect. Histopathological examination errors, especially in the case of needle biopsies can lead to errors in diagnosis and treatment with negative results for the patient.

Understanding orthopedic infections through a different perspective: Microcalorimetry growth curves.

Infectious disease is a serious healthcare problem in orthopedics, as well as other surgical specialties. Accurate and prompt diagnosis, as well as proper care, is critical, as infection of a surgical wound, particularly in the case of arthroplasties or the use of orthopedic implants, can have a catastrophic effect in most cases, necessitating the removal of foreign material. Lyophilized bacteria samples were obtained from Cantacuzino National Institute of Research and Development for Microbiology and Immunology and investigated microcalorimetrically. Isothermal microcalorimetry measures the temperature generated by the multiplication of microorganisms; using an adapted program, it describes the growth curve in real-time according to the received electrical signal. The thermograms of Escherichia coli and Klebsiella pneumonie were analyzed, and similarities were observed for both the time required for the bacteria to grow and the heat flow generated by their growth. Bacterial microcalorimetry has a variety of benefits, and should be regarded as a means of rapid and accurate diagnosis. Sensitivity is a valuable attribute for a diagnostic technique; when only a few microorganisms are present, microcalorimetric signs of bacterial multiplication can be observed. Microcalorimetry has potential as a simple diagnostic tool in a variety of infections, but further research is needed to ensure that it is used correctly. A thorough investigation (including kinetic analysis) of a reproducible thermal signal of bacterial growth could lead to the creation of new methods for quickly identifying bacteria.

Minimally invasive treatment and internal fixation vs. extended lateral approach in calcaneus fractures of thalamic interest.

The extended lateral side approach is a common technique in the surgical treatment of calcaneal fractures, with thalamic collapse offering a good exposure of the fractured site; however, it can be burdened with complications due to soft tissue trauma. The present study aimed to compare patients treated with minimally invasive osteosynthesis through a minimum lateral approach and internal fixation with patients that were treated using internal fixation with an extended lateral side approach in cases of intra-articular calcaneal fractures with thalamic fracture. Patients were evaluated preoperatively and postoperatively by performing clinical and imagistic examinations, with radiography scans of the anterior-posterior calcaneal profile and computer tomography. Furthermore, preoperative and postoperative analyses of the Böhler angle on the radiological profile, complications and duration of the hospital admission for both groups were performed. There were 36 patients (39 calcaneal fractures) in group 1 and 24 patients (29 calcaneal fractures) in group 2. The results demonstrated no statistically significant differences in the preoperative (P=0.72) and postoperative (P=0.20) Böhler angle values. The postoperative Böhler angle average values were 26.9 in group 1 and 29.3 in group 2. A total of 11 patients were treated with Kirschner wires inserted in the calcaneus, and in 2/ll cases, one of the brooches registered a migration movement. There were no cases of material migration in the fractures that were stabilized by inserting Kirschner brooches up to the astragalus and cuboid bones. Taken together, the results of the present study demonstrated no significant differences in the Böhler angle values between the minimally invasive and open reduction techniques. However, the antibiotic therapy period, as well as the infection rate were lower in patients that were treated using the minimally invasive technique, suggesting that this technique was superior with respect to lower complication rates and improved functional results.

LEAM vs. BEAM vs. CLV Conditioning Regimen for Autologous Stem Cell Transplantation in Malignant Lymphomas. Retrospective Comparison of Toxicity and Efficacy on 222 Patients in the First 100 Days After Transplant, On Behalf of the Romanian Society for Bone Marrow Transplantation.

High-dose chemotherapy (HDT) followed by autologous hematopoietic stem cell transplantation (ASCT) is widely used in patients with malignant lymphomas. In Europe over 8,000 ASCTs for lymphoma were performed out of a total of 40,000 transplants according to the European Bone Marrow Transplant (EBMT) activity survey in 2017. ASCT is considered the standard treatment for eligible patients failing to achieve remission after first line chemotherapy or patients with relapsed or refractory lymphomas, including classical Hodkin's lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, and follicular lymphoma, as well as consolidation therapy in first remission in mantle cell lymphoma. BEAM (BCNU/carmustine, etoposide, cytarabine, and melphalan) is the most commonly used conditioning regimen for ASCT in patients with relapsed/refractory (R/R) lymphomas in Europe, whereas the CBV (cyclophosphamide, BCNU, and etoposide) regimen is also widely used in North America. Recently, concerns regarding BCNU toxicity as well as restricted availability of BCNU and melphalan has determined an increasing number of transplant centers to use alternative conditioning regimens. Currently, only a few comparative studies, most of them retrospective, between different conditioning protocols regarding efficacy and toxicity have been published. Thus, in the current manuscript, we report the experience of 2 transplant centers in ASCT in R/R lymphomas with three types of conditioning: BEAM, CLV (cyclophosphamide, lomustine, etoposide) and LEAM (lomustine, etoposide, cytarabine, and melphalan), with the aim to evaluate the results of alternative conditioning regimens using lomustine (LEAM and CLV) and compare them with the standard BEAM regarding early toxicity, engraftment, and transplant related mortality (TRM). All patients developed grade IV neutropenia, anemia with/without transfusion necessity. Severe thrombocytopenia with transfusion requirements is reported in most cases. Median time to platelet engraftment and neutrophil engraftment was 13 days (range) and 10 days (range), respectively. Gastrointestinal toxicity was the most common non-hematologic toxicity after all three conditioning regimens. Oral mucositis in various grades from I to IV was diagnosed in most cases. Other side effects include vomiting, diarrhea, colitis, and skin rash but with low severity grades. For the LEAM arm, one patient died after transplant, before engrafting, one patient didn't achieve platelet engraftment in day 100, one patient developed grade 3 upper gastrointestinal bleeding, one patient died (grade 5 toxicity) with acute renal failure, one patient developed hypoxic events up to grade 4 acute respiratory failure and one patient developed grade 3 itchy skin rash. For the CLV arm, one patient died after transplant, before engrafting, one patient developed grade 3 colitis, one patient with grade 3 hepatic cytolysis, one patient with cardiac toxicity followed by death (grade 5) caused by an acute myocardial infarction with ST elevation and one patient with pulmonary toxicity clinically manifested with grade 3 pleurisy. For the BEAM arm, one patient developed grade 3 cardiac toxicity with sinus bradycardia and afterwards grade 4 with acute pulmonary edema, three patients presented a grade 3 pruritic skin rash and two patients developed grade 3 seizures. In the present study we presented the differences that were observed between BEAM, LEAM, and CLV conditioning regimens offering clinical arguments for an SCT practitioner choice in the ideal situation, but also of choice for alternative regimens in the case that one regimen cannot be used.

Atypical Right Hepatectomy for Liver Metastasis from Ovarian Leiomyosarcoma - A Case Report and Literature Review.

Ovarian leiomyosarcomas are extremely rare ovarian malignancies, usually associated with poor prognosis in terms of survival. Most often, ovarian leiomyosarcomas are diagnosed in postmenopausal women at an advanced stage of disease, the main symptoms consisting of abdominal pain. We present the case of a 52-year-old patient who was initially submitted to surgery for a large ruptured ovarian tumor in April 2009; at that time, total hysterectomy with bilateral adnexectomy, omentectomy, pelvic and para-aortic lymph node dissection were performed. The histopathological studies revealed the presence of an ovarian leiomyosarcoma. Five years later, the patient was diagnosed with a unique, ruptured liver metastasis and an atypical right hepatectomy was performed. The histopathological studies confirmed the metastatic origin of the lesion. At 2-year-follow-up the patient is still free from recurrent disease.

Incidental Finding of a Neuroendocrine Tumor Arising from Meckel Diverticulum During Hernia Repair - A Case Report and Literature Review.

Meckel diverticulum is the most common abnormality of the gastrointestinal tract arising from an incomplete obliteration of the vitelline duct during the intrauterine life. Although tumor development in Meckel diverticulum is not a common situation, it can occur due to the persistence of cellular islets with gastric, pancreatic or intestinal origin. The presence of a neuroendocrine tumor arising from Meckel diverticulum is even scarcer. We present the case of a 59-year-old patient in whom a Meckel diverticulum was found during surgery for inguinal hernia; the histopathological and immunohistochemical studies revealed the presence of a well-differentiated neuroendocrine tumor with low mitotic index.

Haploidentical Donors: Can Faster Transplantation Be Life-Saving for Patients with Advanced Disease?

Haploidentical stem cell transplantation is a therapeutic option for patients without an HLA-matched donor. It is increasingly being used worldwide due to the application of posttransplantation cyclophosphamide and is associated with lower incidence of graft-versus-host disease and treatment-related mortality. Haploidentical donors are generally available for most patients and stem cells can be rapidly obtained. Delays in transplantation while waiting for unrelated donor cells can be potentially problematic for patients with advanced disease at risk for progression; thus, the use of haploidentical donors, especially in this setting, can be life-saving. Here we reviewed the literature on haploidentical stem cell transplantation performed with posttransplantation cyclophosphamide.

The impact of donor liver graft quality on postoperative outcome in liver transplant recipients. A single centre experience.

INTRODUCTION: The Donor Risk Index (DRI) has become a universal score for organ allocation in liver transplantation (LT) worldwide. The aim of this study was to evaluate the impact of liver graft quality measured by DRI, CIT, WIT and donor age on intraoperative hemodynamics (reperfusion syndrome) and early postoperative outcome, defined as initial graft poor function (within 3 days of LT), of deceased donor liver transplant (DDLT) recipients. Secondary end-points were the assessment of the impact of graft quality on the intraoperative and postoperative day 1 hemostasis (evaluated using ROTEM assay). METHODS: We retrospectively analyzed 135 patients who underwent deceased-donor LT between January 2013 and December 2014. Patient demographic data (age, sex, cause of End-Stage Liver Disease), preoperative paraclinical data (total bilirubin, creatinine, serum sodium), severity of liver disease scores (Model for End-Stage Liver Disease - MELD and MELD-sodium), intraoperative blood loss and blood products transfusion, incidence of post reperfusion syndrome, postoperative biochemical data (including total bilirubin, hepatic transaminases, lactate levels) and outcome (initial graft poor function diagnosis) were noted. Donor characteristics including DRI, CIT, WIT and donor age were noted. Coagulation was assessed by rotational thromboelastometry (ROTEM) after reperfusion of the graft and on postoperative day 1 in order to determine the effects of liver graft quality on hemostasis. RESULTS: Donor age has significantly correlated with decreased derived ROTEM parameters time to the maximum velocity of clot formation - MaxVt (p = 0.000), area under the curve (AUC) (p = 0.008) and maximum clot elasticity (MCE) (p = 0.018) although no difference in transfusion requirements has been observed. A longer CIT was associated with an increase in AST and ALT observed during the early postoperative period: day 1 ALT (p = 0.032) and AST (p = 0.008), day 2 ALT (p = 0.001) and AST (p = 0.001) and day 3 AST (p = 0.010) and ALT (p = 0.001). Higher DRI correlated with higher bilirubin levels measured on postoperative day 1 (p = 0.027) and 2 (p = 0.001). Patients who developed initial graft poor function received liver grafts from older donors (p = 0.05) with a higher DRI (p = 0.002). CONCLUSION: Our results suggest a significant impact of donor age and DRI on perioperative coagulation kinetics that may be a result of initial graft poor function. Although CIT and DRI correlated with a more severe cholestasis and hepatocitolysis during the early postoperative period these seems to be short-lived.

Spontaneous portohepatic venous shunt: ultrasonographic aspect.

We aimed to describe the imaging findings of a spontaneous portohepatic venous shunt. This is a rare entity, especially when it is not associated with risk factors such as portal hypertension or liver trauma. We report the case of a 67-year-old woman admitted to our clinic for progressive asthenia, loss of appetite, and progressive upper abdominal pain. We performed several blood tests, abdominal ultrasonography, contrast-enhanced abdominal ultrasonography, and abdominal computed tomographic scan to establish and confirm the diagnosis. Findings of ultrasound revealed a cystic mass in the right liver lobe. Liver enzymes were normal, and viral hepatitis markers as well as serology for Echinococcus granulosus were negative. There were no signs of liver cirrhosis or portal hypertension. Abdominal ultrasound and contrast-enhanced ultrasound established the diagnosis of portohepatic venous shunt; this was also confirmed by abdominal computed tomographic scan. Because the patient did not present any risk factors, the diagnosis was of spontaneous portohepatic venous shunt.

Rhino-cerebral zygomycosis after allogeneic transplant: case report and literature review.

The proportion of patients with hematological malignancies (HM) who develop rare invasive fungal infections (IFI) has increased worldwide over the past few decades. Zygomycosis is an opportunistic fungal infection, which begins in the nose and paranasal sinuses due to inhalation of fungal spores. Rhino-cerebral zygomycosis is the most common form of the disease, it typically develops in diabetic or immunocompromised patients and presents as an acute fulminate infection, which is often lethal. We report a case of rhino-cerebral zygomycosis in an allotransplanted patient to emphasize early diagnosis and treatment of this potentially fatal fungal infection. We discuss different risk factors, specific diagnosis procedures and review the current concepts in management of zygomycosis.