Cancer-Associated Thrombosis: Pathophysiology, Laboratory Assessment, and Current Guidelines.

Dysregulated hemostasis in cancer patients is associated with various clinical conditions, from thromboembolic complications to disseminated intravascular coagulation. Despite the well-established association between cancer and thromboembolic complications, the mechanisms involved are not completely elucidated. There are several predisposing factors in cancer for increased thrombus generation, such as immobilization and chemotherapy. The term cancer-associated thrombosis (CAT) has been introduced to describe the close bidirectional relationship between cancer and thromboembolic events. Conventional coagulation tests (PT/aPTT) are more accurate in detecting a hypocoagulable rather than a hypercoagulable state; thus, their contribution to CAT management is limited. Traditionally, D-dimer levels have been the most common laboratory study for the evaluation of thrombotic risk. However, D-dimer levels only display a snapshot of the coagulation cascade, and they cannot provide a dynamic evaluation of evolving clot formation. Non-conventional assays, such as viscoelastic methods and microparticle formation are promising tools for the identification of patients at risk for developing CAT. Recent guidelines from the American Society of Clinical Oncology counsel against the estimation of thrombotic risk through a single test and recommend the use of scoring systems that take into account several risk factors. The present review outlines the current insights into the pathophysiological mechanisms of CAT and provides a comprehensive review of the latest advances in the laboratory assessment of CAT and the recent guidelines for the management of patients at risk for developing thromboembolic complications.

Infective Endocarditis by Lactobacillus Species-A Narrative Review.

Bacteria of the genus Lactobacillus are microaerophilic or aerotolerant anaerobic Gram-positive non-spore-forming rods. They are considered essential members of the human gut microbiome; however, recent studies have revealed that these microorganisms are less predominant in the gut microbiome than initially thought. Lactobacillus spp. is mainly known for its use as a probiotic in foods and supplements to prevent and treat specific issues such as infectious diseases, irritable bowel syndrome, and diabetes mellitus. However, Lactobacillus spp. may occasionally cause infections such as bacteremia or infective endocarditis (IE). The present study aimed to review all cases of IE by Lactobacillus spp. and describe the epidemiology, microbiology, clinical characteristics, treatment, and outcomes of this infection by collecting relevant data from studies existing in Pubmed and Scopus until 28 September 2023. A total of 77 studies containing data for 82 patients were included. The median age was 56 years, and 69.6% were male. A prosthetic valve was present in 16% of patients, and 17.3% had previously been on probiotics. The aortic valve was the most commonly involved intracardiac site, followed by the mitral valve. Fever, embolic phenomena, sepsis, and heart failure were the most common clinical presentations. Aminoglycosides and penicillin were the most commonly used antimicrobials for definitive treatment. Surgery was performed in 53.7% of patients. Overall mortality was 17.1%. IE in prosthetic valves and presentation with shock were independently associated with overall mortality.

From Clinical Suspicion to Diagnosis: A Review of Diagnostic Approaches and Challenges in Fungal Keratitis.

Fungal keratitis is a relatively rare yet severe ocular infection that can lead to profound vision impairment and even permanent vision loss. Rapid and accurate diagnosis plays a crucial role in the effective management of the disease. A patient's history establishes the initial clinical suspicion since it can provide valuable clues to potential predisposing factors and sources of fungal exposure. Regarding the evaluation of the observed symptoms, they are not exclusive to fungal keratitis, but their timeline can aid in distinguishing fungal keratitis from other conditions. Thorough clinical examination of the affected eye with a slit-lamp microscope guides diagnosis because some clinical features are valuable predictors of fungal keratitis. Definitive diagnosis is established through appropriate microbiological investigations. Direct microscopic examination of corneal scrapings or biopsy specimens can assist in the presumptive diagnosis of fungal keratitis, but culture remains the gold standard for diagnosing fungal keratitis. Advanced molecular techniques such as PCR and MALDI-ToF MS are explored for their rapid and sensitive diagnostic capabilities. Non-invasive techniques like in vivo confocal microscopy (IVCM) and optical coherence tomography (OCT) are useful for real-time imaging. Every diagnostic technique has both advantages and drawbacks. Also, the selection of a diagnostic approach can depend on various factors, including the specific clinical context, the availability of resources, and the proficiency of healthcare personnel.

Hippocrates: A Pioneer in Orthopaedics and Traumatology.

PURPOSE: Hippocrates, the ancient Greek physician, is considered the father of Medicine; however, his contributions to Orthopaedics and Traumatology have not been highlighted enough. The present historical review represents an effort to present and categorize his work, in this field, per clinical disorder and anatomical region. METHODS: The "Hippocratic Corpus" original text was thoroughly studied to identify all Hippocrates' contributions in Orthopaedics and Traumatology. Volume III of his works, especially "On Fractures", "On Joints", and "Mochlicon" includes a plethora of information regarding the management of traumas, as well as other disorders and clinical entities of the musculoskeletal system. RESULTS: In particular, Hippocrates describes reduction techniques for fractures, as well as joint dislocations, elaborates on the biology of the fractures' healing process and the basic principles of fracture management and fixation, presents the signs and symptoms of gangrene, teaches the treatment of osseous infections and offers valuable insight on the biomechanics and treatment of spinal diseases. CONCLUSIONS: Hippocrates' contributions in Orthopaedics and Traumatology are unprecedented, making him a true pioneer in this field, while the basic principles that he presented were further studied and confirmed in the 19th and 20th centuries.

Foot Osteomyelitis Caused by Multidrug- and Extensively Drug-Resistant Gram-Negative Bacteria.

There are scarce data regarding foot osteomyelitis (FO) caused by multidrug-resistant (MDR) and extensively drug-resistant (XDR) Gram-negative bacteria (GNB). This study investigates the causative organisms, the diagnostic and therapeutic approach and the outcome of these infections. All patients with FO caused by MDR and/or XDR GNB who received treatment in the Department of osseous infectious diseases of the "Attikon" University Hospital of Athens, Greece, were recorded and evaluated during a six-year-period. Seventeen patients, of which 64.7% females, with a mean age of 54.06 years were studied. There were nine cases with diabetic (DFO), and 76.5% of patients reported previous use of antimicrobials. Pathogens were isolated from soft-tissue biopsies or intra-operative tissue samples (n=12) and/or affected bone samples (n=5). In most cases, E. coli and P. aeruginosa were isolated (each 29.4%), followed by P. mirabilis (11.7%), while polymicrobial infection was detected in nine patients (53%). Most cases were given antimicrobial monotherapy (88.2%) with a mean duration of 90.05 days, while surgery significantly promoted cure of the infection. Foot and DFO cases represent a challenging to treat disease, requiring a multidisciplinary approach. Surgical treatment remains the cornerstone of treatment, while it is of utmost importance to isolate the causative organisms. MDR and XDR GNB represent an emerging threat and more data are needed to better understand these infections.

Evolution and Progress of mRNA Vaccines in the Treatment of Melanoma: Future Prospects.

mRNA vaccines encoding tumor antigens may be able to sensitize the immune system of the host against cancer cells, enhancing antigen presentation and immune response. Since the breakout of the COVID19 pandemic, interest in mRNA vaccines has been accelerating, as vaccination against the virus served as a measure to limit disease spread. Given that immunotherapy has been the cornerstone of melanoma treatment over the last several decades, further innate immunity enhancement by targeted mRNA vaccines could be the next pivotal achievement in melanoma treatment. Preclinical data coming from murine cancer models have already provided evidence of mRNA vaccines' ability to induce host immune responses against cancer. Moreover, specific immune responses have been observed in melanoma patients receiving mRNA vaccines, while the recent KEYNOTE-942 trial may establish the incorporation of the mRNA-4157/V940 vaccine into the melanoma treatment algorithm, in combination with immune checkpoint inhibition. As the existing data are further tested and reviewed, investigators are already gaining enthusiasm about this novel, promising pathway in cancer therapy.

Evolving Treatment Landscape of HER2-mutant Non-Small Cell Lung Cancer: Trastuzumab Deruxtecan and Beyond.

Successful targeting of HER2-activating mutations in DESTINY-Lung02 phase II study has led to the approval of the antibody-drug conjugate (ADC) trastuzumab deruxtecan (T-DXd) as second-line treatment in patients with non-small cell lung cancer (NSCLC). Despite the impressive results, several matters need to be addressed, including the clinical activity of T-DXd in patients with disease in the central nervous system as well as the role of T-DXd in the context of HER2 overexpression. Additionally, data regarding novel agents used to target HER2 continue to accumulate. This review highlights the challenges and unanswered questions that have emerged after the approval of T-DXd in patients with HER2-mutant NSCLC.

Treatment of Pathological Fracture of Radius due to Multiple Myeloma with Elastic Intramedullary Nail and Cement Augmentation: Expanding the Indications of Elastic Nails.

Pathological fractures of the proximal radius are exceedingly rare. Here, a case of an 81-year-old female diagnosed with multiple myeloma 15 years ago who suffered a pathological fracture of her left proximal radius is presented. Due to the fracture's proximity to the elbow joint and the lack of adjacent healthy bone tissue, a resourceful surgical intervention was implemented using a pediatric flexible nail supplemented by polymethacrylate cement injection. Six weeks post-operatively, the patient had alleviation of the pain with fully functional forearm. This novel approach could possibly aid in the treatment of other long bone pathological fractures due to neoplastic metastases.

Bilateral Spontaneous Supraspinatus Tendon Rupture Under Prolonged BRAF/MEK Targeting Treatment in a Melanoma Patient.

The B-Raf proto-oncogene, serine/threonine kinase (BRAF)/ mitogen-activated protein kinase kinase (MEK) targeting agents have become the treatment of choice for BRAF-mutated melanoma during the last decade. However, it is possible that some long-term adverse events of these drugs have not yet been reported. A case of bilateral spontaneous, non-traumatic, supraspinatus tendon rupture in a 65-year-old Caucasian male suffering metastatic melanoma under prolonged and successful combination treatment with dabrafenib plus trametinib is presented. These damages could not be attributed to some other probable cause. The ruptured tendons were promptly restored arthroscopically. Oncologists should remain vigilant for the early detection of potential side effects of BRAF/MEK targeting agents that have not been systematically recorded yet but may appear and affect patients in the long run.

Infective Endocarditis by Clostridioides and Clostridium Species-A Narrative Review.

Bacteria of the genus Clostridium are anaerobic Gram-positive spore-forming bacilli that include more than 200 species. Some of them are known to cause invasive infections and diseases caused by the production of toxins. Some of the diseases that are mediated by toxins are colitis in patients with specific risk factors, such as previous administration of antimicrobials or foodborne botulism. Invasive diseases include bacteremia, infective endocarditis (IE), clostridial myonecrosis (gas gangrene), and other diseases that involve the destruction of soft tissue due to the local production of toxins. The present study aimed to review all cases of IE by Clostridioides and Clostridium species and describe the epidemiology, clinical characteristics, treatment, and outcomes of these infections. A narrative review was performed based on a search in PubMed and Scopus for studies published until 11 September 2023, providing such data of IE caused by Clostridioides and Clostridium species in humans. A total of 20 studies containing data for 21 patients were included. A prosthetic valve was present in 5 patients (23.8%). The aortic valve was the most commonly involved, followed by the mitral valve. Fever, sepsis, and embolic phenomena were the most common clinical presentations. Beta-lactams and metronidazole were the most commonly used antimicrobials. Surgery was performed in nine patients (45%). Mortality reached 33.3%. IE in multiple valves was associated with increased mortality. Despite the heterogeneous genetic and molecular characteristics that necessitate the taxonomic change of some of this genus's previous members, the clinical syndrome of IE caused by these bacteria seems to have similar characteristics.

Soleus Muscle Single Metastasis from Hepatocellular Carcinoma.

Extrahepatic metastases of hepatocellular carcinoma (HCC) are associated with poor prognosis, while such lesions in skeletal muscles are extremely rare. A unique case of skeletal metastasis in the soleus muscle in a 76-year-old male patient with HCC is reported. The patient presented with a painful palpable mass in his left calf. Magnetic resonance imaging (MRI) revealed a contrast-enhancing lesion in the soleus muscle, while core needle biopsy showed metastatic lesion from the HCC. Due to the poor overall condition of the patient, no further treatment was performed, while he passed away three months later. Hepatocellular carcinoma represents an aggressive tumor, with poor prognosis, especially in cases of extra-hepatic metastases. Such lesions have a reported incidence of about 15%. Extra-hepatic metastasis to the skeletal muscles is extremely rare, with only 21 more such cases reported in the literature so far. No clear therapeutic strategies exist for such cases. Thus, it is of utmost importance to detect similar cases in early stages for a possible better prognosis and clearer understanding of the therapeutic options, including surgical and loco-regional treatments.

Severe Gastritis Due to Nivolumab Treatment of a Metastatic Melanoma Patient.

Nivolumab, an anti-PD-1 check point inhibitor, is an immunotherapeutic agent, representing a major step in the treatment of melanoma. However, its use is associated with severe toxicities. Among them, gastrointestinal (GI) disorders from the lower GI tract have been widely reported. On the contrary, disorders from the upper GI tract are rare. Such a case of delayed nivolumab induced severe gastritis in a 53-year-old Caucasian female patient suffering metastatic melanoma is described. The patient's symptoms from the upper GI tract began 4 months after nivolumab treatment initiation. The diagnosis was based on imaging, including PET/CT, endoscopical and pathological findings. The side effect was successfully treated with prolonged administration of proton pump inhibitors and corticosteroids. There are only a few cases of immune check point inhibitors (ICPis) induced upper GI tract disorders, while it seems that the symptoms from nivolumab induced upper GI tract damages appear later than those reported in the lower part. Nivolumab, among other side effects, may cause severe gastritis. Hence, this pathological entity should be included in the list of this drug's side effects.

Prosthetic Knee Joint Infection Due to Candida lusitaniae: A Diagnostic and Therapeutic Odyssey: A Case Study.

Prosthetic joint infections (PJIs) caused by fungi, although relatively rare, represent a major surgery-related complication. An extremely rare fungal PJI, following revised total knee replacement (TKR) caused by Candida lusitaniae, is reported, and a meticulous review of similar cases is provided. A 74-year-old female, who underwent primary total knee arthroplasty 10 years ago and a revision surgery three weeks ago, presented with signs and symptoms of PJI. C. lusitaniae was eventually isolated from the periprosthetic tissue using the MALDI-TOF VitekMS-bioMérieux technique. Multiple strategies for managing this fungal PJI were performed, and finally, the patient was treated successfully with an intramedullary arthrodesis system and proper antifungal treatment, including fluconazole. A multidisciplinary approach is essential for the diagnosis and treatment of such severe infections. In persistent cases and in cases where revision surgery is extremely difficult to perform, arthrodesis seems to be an effective solution for the elimination of the infection. The efficacy of the therapeutic management of fungal PJIs remains unclear. Therefore, more research should be reported, focusing on proper treatment so that the optimal strategy in treating these severe infections may be established.

The "Phoenix Jaw" Phenomenon Revisited: Two Cases of Bisphosphonate-Related Mandible Osteonecrosis Surgically Treated with Complete Bone Regeneration.

Bisphosphonate-related osteonecrosis of the jaws represents a well-recognized complication occurring in patients being administered drugs for the treatment of osteoporosis and/or malignant disease. Treatment of this condition, aiming to alleviate the symptoms and restore functional status, represents a challenge for the maxillofacial surgeon. Conservative management has been proposed for early stages of this condition, while surgical intervention is mandatory for advanced disease. Two cases of severe bisphosphonate-related osteonecrosis of the jaw that achieved complete osseous recontouring after partial mandibulectomy, are presented.

Fungal Prosthetic Joint Infection in Revised Knee Arthroplasty: An Orthopaedic Surgeon's Nightmare.

Fungal prosthetic joint infections (PJIs), despite the fact that they are rare, represent a devastating complication. Such infections in revised knee arthroplasties pose a unique surgical and medical challenge. A rare case of Candida parapsilosis PJI in revised knee arthroplasty is reported. Furthermore, a thorough review of all published fungal PJIs cases in revised knee arthroplasties is provided. A 72-year-old female with total knee replacement surgery due to osteoarthritis 10 years ago, followed by two revision surgeries six and two years ago due to aseptic loosening, presented with signs and symptoms of septic loosening of the knee components. Resection arthroplasty and cement-spacer placement was performed and periprosthetic tissue cultures yielded Candida parapsilosis. The patient was commenced on proper antifungal treatment (AFT) for six months and then the second stage of the revision surgery was performed successfully. From 2000 to 2022, a total of 46 patients with median age 69 years [interquartile range (IQR = 10)], suffering fungal PJI occurring in revised knee arthroplasty have been reported. The median time from initial arthroplasty to symptoms' onset was 12 months (IQR = 14). Cultures of local material (52.2%) and histology (6.5%) were the reported diagnostic method, while Candida species were the most commonly isolated fungi. Regarding surgical management, two-stage revision arthroplasty (TSRA) was performed in most cases (54.3%), with median time-interval of six months (IQR = 6) between the two stages. Regarding AFT, fluconazole was the preferred antifungal compound (78.3%), followed by voriconazole and amphotericin B (19.6% each). The median duration of AFT was five months (IQR = 4.5). Infection's outcome was successful in 38 cases (82.6%). Fungal PJIs, especially in revised knee arthroplasties, are devastating complications. A combination of AFT and TSRA seems to be the treatment of choice. TSRA in these cases poses a special challenge, since major bone defects may be present. Therapeutic procedures remain unclear, thus additional research is needed.

Therapeutic Effect of mRNA SARS-CoV-2 Vaccine on Melanoma Skin Metastases.

A unique case of multiple metastatic melanoma skin nodules regression in a heavily pretreated, 72-year-old Caucasian female, after administering the second dose of the SARS-CoV-2 mRNA Pfizer-BioNTech vaccine, is presented. Two days after vaccination, all her melanoma skin nodules became painful and were significantly reduced in size. Physical examination and ultrasound imaging confirmed the patient's observation. The effect was sustained, and further reduction of the nodules occurred after the third vaccine dose. One of the reduced nodules was removed, histologically examined, and its histopathology was compared to that of another such nodule removed and examined earlier. Distinct differences were observed between the two histopathologies, with the most notable the unexpected finding of the absence of infiltrating lymphocytes in the reducer nodule's melanoma tissue. Based on this observation, the possible immunological mechanism(s) leading to the vaccine's effect are speculated. More possible is the vaccine's antitumor and apoptotic activity via stimulation of the Tol Like Receptors 3, 7, and 8, and (downstream) the nuclear factor kappa-light-chain-enhancer of the activated B cells pathway of the non-lymphocytic immune effector cells.

Joseph Lister (1827-1912): A Pioneer of Antiseptic Surgery.

Joseph Lister was a prominent British surgeon and medical scientist who established the study of antisepsis. Applying Louis Pasteur's germ theory of fermentation on wound putrefaction, he promoted the idea of sterilization in surgery using carbolic acid (phenol) as an antiseptic. His method reduced the incidence of wound sepsis and gangrene, which, in turn, reduced the need for amputation. By showing how germs could be prevented from entering the wound, Lister increased the safety of surgical operations and laid the foundations for all subsequent advances in the field.

Native Joint Infections by Aspergillus Species.

BACKGROUND: Septic arthritis due to Aspergillus spp. represents a rare, but severe disease. Nevertheless, clear guidelines regarding most effective medical treatment have not yet been established. The present study is a literature review of all reported cases of fungal septic arthritis due to Aspergillus spp, in order to clarify epidemiology, as well as the medical and operative management and their outcome. METHODS: A meticulous review of all published septic arthritis infections due to Aspergillus has been conducted. Information regarding demographics, causative fungus, antifungal treatment (AFT), surgical intervention, as well as the infection's outcome were recorded and evaluated. RESULTS: A total of 30 Aspergillus spp. strains from 29 hosts have been studied. The patients' mean age was 45.8 years. The most commonly affected joint was the knee (45.7%), while the predominant symptom was joint pain (62%). Most patients were immunocompromised (72.4%). Diagnosis was established through cultures and/or histopathology. Aspergillus fumigatus was the most common responsible fungi (63.3%), followed by A. flavus (16.6%) and A. terreus (10%). Regarding AFT, the preferred agent proved to be Amphotericin B (14 cases; 48.3%), followed by voriconazole (11; 37.9%), while the mean AFT duration was 5.6 months. In most cases surgical treatment was also performed (in 4 cases no surgery was reported). Treatment was effective in 20 cases (69%). CONCLUSIONS: Septic arthritis caused by Aspergillus spp. represents a severe clinical entity. It seems that, with the available data, prolonged AFT along with surgical intervention is the preferred management of this infection, while identification of the responsible fungus is of utmost importance.

Spondylodiscitis Caused by Aspergillus Species.

BACKGROUND: Spondylodiscitis caused by Aspergillus spp. is a rare but life-threatening clinical entity. However, a consensus on diagnostic criteria and most effective medical management is still missing. The present study is a review of all published cases of spondylodiscitis caused by Aspergillus spp., in an effort to elucidate epidemiology, patients' characteristics, andand the medical and surgical treatment options and their effectiveness. METHODS: A thorough review of all existing spondylodiscitis cases caused by Aspergillus was performed. Data regarding demographics, responsible fungus, time between symptoms' onset and firm diagnosis, antifungal treatment (AFT), surgical intervention, andand the infection's outcome were investigated. RESULTS: A total of 118 Aspergillus spondylodiscitis cases, yielding 119 Aspergillus spp. isolates, were identified in the literature. The patients' mean age was 40.6 years. Magnetic resonance imaging (MRI) (after its introduction) indicated the diagnosis in most cases (66.7%), while definite diagnosis was established through cultures in the majority of cases (73.7%). Aspergillus fumigatus was isolated in most cases (73; 61.3%), followed by Aspergillus flavus (15; 12.6%) andand Aspergillus nidulans and terreus (7; 5.9%, each). The mean time between symptoms' onset and diagnosis was 5.7 months. Amphotericin B was the preferred antifungal regiment (84 cases; 71.2%), followed by voriconazole (31; 26.3%), and the mean AFT duration was 6.1 months. The final outcome was successful in 93 cases (78.8%). Furthermore, 77 patients (65.3%) underwent surgery. CONCLUSIONS: Spondylodiscitis caused by Aspergillus spp. represents a clinical challenge, requiring a multidisciplinary approach. The present review has shown that prolonged AFT has been the standard of care of the studied cases, while surgical treatment seems to play an important role in selected patents.

Acute paraplegia due to thoracolumbar schwannoma following trauma: A case report and literature review.

Spinal schwannomas account for one third of primary spinal neoplasms. Clinical presentation is related to the tumor location. An atypical case of acute paraplegia following a fall, on the ground of a thoracolumbar schwannoma, without intratumoral hemorrhage, in a previously asymptomatic patient is reported. A 58-year-old male patient presented with acute paraplegia, and urinary and bowel incontinence, following a fall. The patient had no previous history of back and/or leg pain or neurological symptoms. Magnetic resonance imaging revealed a subdural mass, as well as a fracture of the right T12-L1 facet joint and the right transverse process. The patient underwent emergency T11-L1 wide laminectomy, exploration of the subdural space and T10-L2 posterolateral transpedicular stabilization and fusion. An intradural, extramedullary mass, causing severe cord compression, was found and excised. Pathology revealed schwannoma, without intratumoral hemorrhage. The patient recovered completely 6 months postoperatively. To the best of our knowledge, this is the first report of spinal intradural schwannoma causing sudden paraplegia in a previously asymptomatic patient in the setting of trauma, without intratumoral hemorrhage. Emergency canal decompression and complete excision of the tumor represent the optimal management of such cases.