Evaluation of Some Prognostic Biomarkers in Human Papillomavirus-Related Multiphenotypic Sinonasal Carcinoma.

Background: Human papillomavirus (HPV)-related multi phenotypic sinonasal carcinoma (HMSC) is a recently described tumor subtype with an unknown prognosis, often misdiagnosed with other sinonasal carcinomas, and associated with high-risk HPV (HR-HPV). The present study aimed to evaluate the expression of vascular endothelial growth factor (VEGF), Bcl-2-associated X protein (BAX), epidermal growth factor receptors (EGFR), ProExTMC, and human telomerase reverse transcriptase (hTERT) and assess their association with survival and clinicopathological characteristics. Methods: Between 2017 and 2022, 40 HMSC patients underwent surgical resection at the School of Medicine, Zagazig University Hospitals (Zagazig, Egypt). Tissue samples were examined for the presence of HR-HPV; absence of myeloblastosis (MYB), MYB proto-oncogene like 1 (MYBL1), and nuclear factor I/B (NFIB) fusions and the presence of myoepithelial proteins (calponin, S100, SMA), squamous differentiation markers (p63, p40, calponin), VEGF, BAX, ProExTMC, and hTERT by immunohistochemistry. All patients were followed up for about 54 months until death or the last known survival data. Data were analyzed using the Chi square test and Kaplan-Meier method. Results: The expression of VEGF, hTERT, and ProExTMC was significantly associated with age, advanced tumor stages, lymph node metastasis, tumor size, mortality, relapse, poor disease-free survival (DFS), and overall survival (OS) (P<0.001). BAX expression was significantly associated with tumor size, age, poor DFS, and relapse (P=0.01, P<0.001, P=0.035, and P=0.002, respectively). Conclusion: HMSC is strongly associated with HR-HPV. The expression of VEGF, EGFR, BAX, hTERT, and ProExTMC is associated with aggressive malignant behavior, poor survival, and poor prognosis, making them novel prognostic biomarkers for targeted therapeutics in HMSC.

Bowel perforation with generalised peritonitis secondary to recurrent primary fallopian tube carcinoma after 17 years.

We describe a case of bowel perforation secondary to a recurrence of primary fallopian tube carcinoma treated more than a decade ago. A woman in her 70s presented to a rural centre with an acute abdomen. An abdominal CT showed a perforated ileum secondary to a pelvic mass. Emergency laparotomy identified the pelvic mass that was adherent to the side wall and invading the ileum at the site of perforation. Its adherence to the external iliac vessels posed a challenge to achieve en-bloc resection; therefore, a defunctioning loop ileostomy was created. Final histopathology and immunopathology were consistent with the recurrence of her primary fallopian tube carcinoma. The patient was further discussed in a multidisciplinary team meeting at a tertiary referral hospital. This case highlighted the importance of having a high index of suspicion for cancer recurrence, the utility of rapid source control laparotomy and multidisciplinary team patient management.

The spleen is the graveyard of CD4+ cells in patients with immunological failure of visceral leishmaniasis and AIDS.

BACKGROUND: Visceral leishmaniasis (VL), or kala-azar, is a common comorbidity in patients with AIDS in endemic areas. Many patients continue to experiences relapses of VL despite virological control, but with immunological failure. These patients remain chronically symptomatic with hypersplenism, for example with anemia, leukopenia, and thrombocytopenia, and are at risk of severe co-infection due to low CD4+ count. Therefore, in this study, splenectomized patients with VL and HIV infection were investigated to understand why the CD4+ count fails to recover in these patients, evaluating the importance of spleen mass for hypersplenism and immunological failure. METHODS: From a retrospective open cohort of 13 patients who had previously undergone splenectomy as salvage therapy for relapsing VL, 11 patients with HIV infection were investigated. This study compared the patients' complete blood cell count (CBC) and CD4+ and CD8+ cell counts before and after splenectomy with respect to spleen weight. RESULTS: CBC was substantially improved after splenectomy, indicating hypersplenism. However, to the best of our knowledge, this is the first study to show that spleen mass is strongly and negatively correlated with CD4+ cell count (ρ = -0.71, P = 0.015). CONCLUSIONS: This finding was unexpected, as the spleen is the most extensive lymphoid tissue and T-lymphocyte source. After reviewing the literature and reasoning, we hypothesized that the immunological failure was secondary to CD4+ loss initially by apoptosis in the spleen induced by productive HIV infection and, subsequently, by pyroptosis sustained by parasitic infection in spleen macrophages.

Transplantation: platform to study recurrence of disease.

Beyond the direct benefit that a transplanted organ provides to an individual recipient, the study of the transplant process has the potential to create a better understanding of the pathogenesis, etiology, progression and possible therapy for recurrence of disease after transplantation while at the same time providing insight into the original disease. Specific examples of this include: 1) recurrence of focal segmental glomerulosclerosis (FSGS) after kidney transplantation, 2) recurrent autoimmunity after pancreas transplantation, and 3) recurrence of disease after orthotopic liver transplantation (OLT) for cirrhosis related to progressive steatosis secondary to jejuno-ileal bypass (JIB) surgery. Our team has been studying these phenomena and their immunologic underpinnings, and we suggest that expanding the concept to other pathologic processes and/or transplanted organs that harbor the risk for recurrent disease may provide novel insight into the pathogenesis of a host of other disease processes that lead to organ failure.

Statin Therapy for Secondary Prevention in Ischemic Stroke Patients With Cerebral Microbleeds.

BACKGROUND AND OBJECTIVES: The association between statin use and the risk of intracranial hemorrhage (ICrH) following ischemic stroke (IS) or transient ischemic attack (TIA) in patients with cerebral microbleeds (CMBs) remains uncertain. This study investigated the risk of recurrent IS and ICrH in patients receiving statins based on the presence of CMBs. METHODS: We conducted a pooled analysis of individual patient data from the Microbleeds International Collaborative Network, comprising 32 hospital-based prospective studies fulfilling the following criteria: adult patients with IS or TIA, availability of appropriate baseline MRI for CMB quantification and distribution, registration of statin use after the index stroke, and collection of stroke event data during a follow-up period of ≥3 months. The primary endpoint was the occurrence of recurrent symptomatic stroke (IS or ICrH), while secondary endpoints included IS alone or ICrH alone. We calculated incidence rates and performed Cox regression analyses adjusting for age, sex, hypertension, atrial fibrillation, previous stroke, and use of antiplatelet or anticoagulant drugs to explore the association between statin use and stroke events during follow-up in patients with CMBs. RESULTS: In total, 16,373 patients were included (mean age 70.5 ± 12.8 years; 42.5% female). Among them, 10,812 received statins at discharge, and 4,668 had 1 or more CMBs. The median follow-up duration was 1.34 years (interquartile range: 0.32-2.44). In patients with CMBs, statin users were compared with nonusers. Compared with nonusers, statin therapy was associated with a reduced risk of any stroke (incidence rate [IR] 53 vs 79 per 1,000 patient-years, adjusted hazard ratio [aHR] 0.68 [95% CI 0.56-0.84]), a reduced risk of IS (IR 39 vs 65 per 1,000 patient-years, aHR 0.65 [95% CI 0.51-0.82]), and no association with the risk of ICrH (IR 11 vs 16 per 1,000 patient-years, aHR 0.73 [95% CI 0.46-1.15]). The results in aHR remained consistent when considering anatomical distribution and high burden (≥5) of CMBs. DISCUSSION: These observational data suggest that secondary stroke prevention with statins in patients with IS or TIA and CMBs is associated with a lower risk of any stroke or IS without an increased risk of ICrH. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with IS or TIA and CMBs, statins lower the risk of any stroke or IS without increasing the risk of ICrH.

[Clinical analysis of 14 patients aged ≤ 50 years with high-risk multiple myeloma treated with allogeneic hematopoietic stem cell transplantation].

Objective: To evaluate the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) in young patients with high-risk multiple myeloma (HRMM) and analyzed the factors affecting patient prognosis. Methods: In this retrospective study, we analyzed the clinical data of 14 patients with HRMM with cytogenetic abnormalities or high-risk biological factors who underwent allo-HSCT at the Hematopoietic Stem Cell Transplantation Center of the Institute of Hematology & Blood Diseases Hospital between November 2016 and November 2022. Results: There were seven males and seven females included in the study, with a median age of 39.5 (31-50) years at the time of allo-HSCT. The median number of treatment lines before transplantation was 2 (1-6) . Before allo-HSCT, 42.9% (6/14) of the patients did not achieve complete remission, while 35.7% (5/14) of the patients achieved measurable residual disease positivity. After transplantation, all patients were evaluated for their treatment response, and the overall response rate was 100% (14/14) . All 14 patients successfully underwent allo-HSCT, with median engraftment times for neutrophils and platelets of 11 (10-14) days and 13 (9-103) days, respectively. Acute grade Ⅱ-Ⅳ graft-versus-host disease (GVHD) occurred in five patients (35.7%) , and two patients (14.3%) developed moderate-to-severe chronic GVHD. The median follow-up time after allo-HSCT was 18.93 (4.10-72.53) months, with an expected 2-year transplant-related mortality rate of 7.1% (95% CI 0%-21.1%) and an expected 2-year overall survival rate of 92.9% (95% CI 80.3%-100.0%) . Moreover, the expected 1-year and 2-year progression-free survival rates were 92.9% (95% CI 80.3%-100.0%) and 66.0% (95% CI 39.4%-100.0%) , respectively, and the 2-year cumulative incidence of relapse was 28.9% (95% CI 0%-56.7%) . Upfront allo-HSCT following complete remission after induced therapy and the presence of chronic GVHD might be favorable prognostic factors. Conclusion: allo-HSCT is an effective treatment for improving the prognosis of young patients with HRMM.

A Rare Coexistence: Cutaneous Lobular Carcinoma with Pyoderma Gangrenosum.

BACKGROUND Pyoderma gangrenosum (PG) is a neutrophilic inflammatory disease associated with inflammatory and autoimmune conditions and malignancies. Previously identified links between PG and cancer have included hematological malignancies, solid-organ tumors such as gastric adenocarcinoma, and breast cancer. While specific histologic subtypes of breast cancer such as ductal carcinoma have been associated with PG of the extremities, the literature is limited on the association between PG and cutaneous metastatic lobular carcinoma. CASE REPORT We describe the case of an 84-year-old woman with recurrent cutaneous metastatic lobular carcinoma of the left anterior chest with concurrent pyoderma gangrenosum on her bilateral lower extremities. The patient was initially diagnosed with lobular carcinoma of the breast and underwent a left breast mastectomy and was in remission. One year later, she developed 2 lower-extremity ulcerations, which at the time were attributed to an injury and underlying venous stasis. She was referred to a wound care clinic, where the lesions worsened with surgical debridement. Six years later, she presented to the dermatology clinic with a rash on her chest wall and worsening of the ulcerations on her ankles bilaterally. Biopsies revealed lobular carcinoma metastatic to the skin of her anterior chest wall and histopathology consistent with pyoderma gangrenosum on her ankles. CONCLUSIONS This case demonstrates a unique presentation of worsening pyoderma gangrenosum due to metastatic malignancy in conjunction with a cutaneous manifestation of lobular carcinoma.

Prognosis and prognostic factors of lung cancer complications in patients with rheumatoid arthritis.

AIM: To clarify the prognosis and prognostic factors for lung cancer in patients with rheumatoid arthritis (RA). METHODS: In this retrospective longitudinal study, we investigated the medical records of patients with RA among 1422 patients diagnosed with lung cancer and registered in a hospital-based cancer registry between January 2013 and May 2022. The Kaplan-Meier method and Cox proportional hazards model were used to analyze survival and identify predictive factors. RESULTS: Of 26 patients with RA complicated with lung cancer (median age, 69 years), the 2-year overall survival rates for stages I-II were 90%-100%, and those for stages III-IV were 20%, respectively. Positivity of anti-citrullinated protein/peptide antibody, smoking history, interstitial lung disease, poorly controlled RA, stage III and IV lung cancer, histological types other than adenocarcinoma and squamous cell carcinoma, and RF ≧ 50 IU/mL were associated with increased mortality. After the surgical resection of stage I and II lung cancer, 5 of the 16 patients experienced cancer recurrence after resumption of RA treatment, and the histology of the recurrent cancers was mostly squamous cell carcinoma. CONCLUSIONS: Early detection of lung cancer is needed, especially in patients with RA who have a history of smoking, seropositivity, or interstitial lung disease. Even after surgical resection, it should be noted that squamous cell carcinoma is prone to recurrence.

Detection of antibody subclasses IgA, IgM and IgG against HPV L1 in HPV-positive oropharyngeal squamous cell carcinoma patients: a pilot study.

PURPOSE: Despite prognostic superiority of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC), up to 25% of patients will suffer from recurrence within the first 5 years. Therefore, it is of great scientific interest to find relevant biomarkers to identify patients at risk. In this prospective observational study, we aimed to investigate the dynamics of HPV-L1 capsid protein specific antibody (AB) subclasses IgA, IgM, and IgG in HPV-positive OPSCC patients under therapy. METHODS: Serum samples from HPV-positive OPSCC patients, identified by positive p16-immunohistochemistry, were collected before and during tumor-specific therapy and 3-6 months during follow-up. They were analyzed for the presence of HPV-L1 AB subclasses IgA, IgM, and IgG using an HPV-L1-specific immuno-assay. Additionally, a PCR-based HPV-DNA detection from the tumor tissue was performed. RESULTS: Altogether, 33 patients with a mean follow-up of 55 months were included. Analysis of a total of 226 serum samples revealed that the most common L1-AB-subclass pattern was characterized by IgG > > IgA > IgM without significant fluctuation during the course of disease. Patients with excessive IgG levels tended to higher tumor stages and three out of three patients with disease recurrence showed increasing IgG AB titers beforehand. Seven patients showed an IgA dominance at diagnosis, which was associated with a better disease-free survival. CONCLUSION: Despite limited cases, our prospective pilot study revealed promising trends in HPV L1 AB subclasses and may contribute useful information for future risk stratification and post-treatment monitoring in HPV-positive OPSCC patients.

Occult solitary fibrous tumour of the pleura presenting as recurrent spontaneous pneumothorax.

A woman in her 30s, non-smoker, presented at the emergency department two times because of spontaneous pneumothorax. The first episode was treated with small bore catheter drainage, while during the second episode-occurring only 1 week later-thoracoscopic talcage was attempted. The postoperative course was characterised by slow clinical and radiological resolution, and recurrence 3 days after discharge. Eventually, multiportal video-assisted thoracoscopic exploration identified an interfissural solid mass. Resection and further work-up revealed the diagnosis of 'low-risk' solitary fibrous tumour (SFT) stage pT1N0M0. The interdisciplinary tumour board advised no adjuvant therapy. A CT thorax was scheduled in 1 year for follow-up. The patient was discharged without complications and has had no recurrences of pneumothorax at 6 months of follow-up. This report shows that SFT can easily be missed on initial presentation and should be considered in the differential diagnosis of pneumothorax, especially when frequently recurring.

Dizzy spells in pregnancy: successful antenatal removal of a huge left atrial myxoma with mitral valve obstruction.

Diagnosing atrial myxoma in pregnancy is challenging because patients may present with non-specific symptoms that might be overlooked. The timing of non-obstetric operation usually depends on the nature of the disease, after careful consideration of feto-maternal safety, including the use of cardiopulmonary bypass and placental transfer of anaesthetic drug. A woman in her 30s at 18 weeks of pregnancy presented with recurring dizziness. She underwent successful myxoma excision at 20 weeks under general anaesthesia and cardiopulmonary bypass. The 6×5 cm myxoma was histologically confirmed as myxoma. Early detection of atrial myxoma in pregnancy is crucial, and a clinician has to consider the diagnosis of left atrial myxoma with mitral valve obstruction as a cause of severe dizziness. Optimal outcomes require multidisciplinary management. In this case, surgery during the second trimester of pregnancy enabled a full-term pregnancy with the patient's and foetal well-being and normal postprocedural echocardiography.

Treatment of Medication-Related Osteonecrosis of the Jaws without Segmental Resections: A Case Series.

BACKGROUND Medication-related osteonecrosis of the jaw (MRONJ) is a rare but serious reaction to anti-resorptive drugs (ARDs) in patients treated for osteoporosis and conditions related to cancer. Treatment for MRONJ consists of the use of non-operative therapies according to the evolution of the disease, which consist of the use of antimicrobial mouthwashes, systemic antibiotics, and operative therapies, such as debridement of necrotic bone, marginal or segmental resection, and bone reconstruction of the jaws in more advanced stages of the disease. CASE REPORT This is a case series of 11 female patients treated for MRONJ, with a mean age of 76.5 years. Patients with malignant diseases of the jaws or those undergoing head and neck radiotherapy were excluded. Nine patients were medicated for osteoporosis with oral bisphosphonates and denosumab, and 2 patients used zoledronate to treat metastatic breast cancer. MRONJ prevailed in the mandible, most patients were classified as stage 2, and the most frequent triggers were tooth extraction and prosthetic trauma. All patients initially underwent non-operative therapies and were operated according to MRONJ stage, but none required segmental resection. Adjuvant treatments were used in 5 patients, and mean treatment and follow-up periods were 5 and 18.3 months, respectively. There was complete resolution of disease in all patients, with only 1 relapse. CONCLUSIONS This case series suggests that it is possible to treat MRONJ with conservative therapies in the early stages of the disease and minimally invasive surgeries in more advanced stages of the disease, thus avoiding segmental jaw resections.

Efficacy and Safety Analysis of Emergency Endoscopic Self-Expanding Metal Stent Placement Without Fluoroscopic Assistance for Right-Sided Colonic Cancer Obstruction.

BACKGROUND: Traditionally, surgical treatment is recommended for right-sided colonic cancer obstruction (RCCO); however, the literature comparing surgical or non-surgical procedures is lacking. METHODS: Patients included in this study were divided into two groups: one group received elective surgery after self-expanding metal stent (SEMS) placement, i.e., the bridge to surgery (BTS) group, and one group received emergency surgery (ES). RESULTS: Thirty-five patients were included in the BTS group and 60 patients underwent ES. The technical and clinical success rates for SEMS placement were 100% and 88.6%, respectively, while the short-term complication rates were 51.4% and 33.3% for the BTS and ES groups, respectively (p = 0.082). Overall, 2.9% and 3.3% of postoperative deaths occurred in the BTS and ES groups (p = 1.000). The 1-year overall survival (OS) rates were 91.4% and 88.3% (p = 0.840), 3-year OS rates were 85.7% and 81.7% (p = 0.860), and 5-year OS rates were 82.9% and 76.7% (p = 0.620) in the BTS and ES groups, respectively. No tumor recurrence was found in the BTS group but seven recurrences were found in the ES group (11.7%) [p = 0.091]. Laparoscopic surgery was chosen by 42.9% of patients in the BTS group and 26.7% of patients in the ES group (p = 0.104); however, the length of hospital stay (p = 0.001) was longer in the BTS group. CONCLUSIONS: In the two groups, no differences were found in terms of postoperative complications and mortality as well as OS. The BTS group preferred to perform laparoscopic surgery and the technical success rate of stenting was high, therefore SEMS for RCCO was considered safe and feasible.

Incidental Coronary Arterial Calcification for Cardiovascular Risk Assessment in Men With Prostate Cancer Undergoing PET/CT Imaging.

BACKGROUND: Cardiovascular (CV) disease is common among men with prostate cancer and the leading cause of death in this population. There is a need for CV risk assessment tools that can be easily implemented in the prostate cancer treatment setting. METHODS: Consecutive patients who underwent positron emission tomography/computed tomography (PET/CT) for recurrent prostate cancer at a single institution from 2012 to 2017 were identified retrospectively. Clinical data and coronary calcification on nongated CT imaging were obtained. The primary outcome was major adverse CV event (MACE; myocardial infarction, coronary or peripheral revascularization, stroke, heart failure hospitalization, or all-cause mortality) occurring within 5 years of PET/CT. RESULTS: Among 354 patients included in the study, there were 98 MACE events that occurred in 74 patients (21%). All-cause mortality was the most common MACE event (35%), followed by coronary revascularization/myocardial infarction (26%) and stroke (19%). Coronary calcification was predictive of MACE (HR = 1.9, 95% CI: 1.1-3.4, P = .03) using adjusted Kaplan-Meier analysis. As a comparator, the Framingham risk score was calculated for 198 patients (56%) with complete clinical and laboratory data available. In this subgroup, high baseline Framingham risk (corresponding to 10-year risk of CV disease > 20%) was not predictive of MACE. CONCLUSIONS: MACE was common (21%) in men with recurrent prostate cancer undergoing PET/CT over 5 years of follow-up. Incidental coronary calcification on PET/CT was associated with increased risk of MACE and may have utility as a CV risk predictor that is feasible to implement among all prostate cancer providers.

Unusual presentation of talonavicular joint pigmented villonodular synovitis: a case report.

BACKGROUND: Pigmented villonodular synovitis is a rare yet locally invasive disorder impacting synovial tissues. This case report delineates the atypical manifestation of pigmented villonodular synovitis in the talonavicular joint, detailing its diagnostic complexity and successful management. CASE PRESENTATION: A 56-year-old Iranian patient with a 4-year history of chronic ankle pain, initially diagnosed with degenerative joint disease post-trauma based on imaging, underwent talonavicular fusion surgery. An unexpected pigmented villonodular synovitis mass was encountered during the procedure. Subsequent interventions encompassed tumor resection, talonavicular joint fusion, and allograft bone grafting. Despite the initial intervention, persistent pain and nonunion necessitated a secondary procedure, involving joint surface curettage and autograft bone grafting. At the 12-month follow-up, the patient remained pain-free without tumor recurrence. CONCLUSION: This case report highlights the significance of considering pigmented villonodular synovitis as a crucial differential diagnosis in chronic ankle pain, even when there is evidence of degenerative joint disease and a history of trauma. Magnetic resonance imaging serves a crucial role in accurate diagnosis. Treatment necessitates precise tumor removal, appropriate bone grafting techniques and secure fixation. LEVEL OF EVIDENCE: IV.

Clinical features and risk factors for postoperative recurrence in patients with Cushing's syndrome of different etiologies.

The clinical characteristics of Cushing's syndrome (CS) vary with etiology, and few studies have investigated the risk factors affecting CS recurrence after surgery. This retrospective study involved 202 patients diagnosed with CS between December 2012 and December 2022. The patients were divided into three groups according to etiology: Cushing's disease (CD), adrenocortical adenoma (ACA), and ectopic adrenocorticotropic hormone (ACTH) syndrome (EAS). Of the patients with CS, 41.9% had hypokalemia and 15.0% had hypophosphatemia. The cortisol levels were negatively correlated with blood potassium, blood chlorine, and blood phosphorus. Moreover, 22.4% of patients had an abnormal heart structure, 11.2% had centripetal remodeling, 5.6% had centripetal hypertrophy, and 5.6% had centrifugal hypertrophy. The overall recurrence rate of CS caused by pituitary tumors and adrenal adenoma was 25.7%. The recurrence times were longer in the ACA group versus the CD group, in patients < 50 years of age versus in patients ≥ 50 years old group, and in patients with CD with tumors ≥ 1 cm versus tumors < 1 cm. Age, preoperative cortisol level, postoperative cortisol level, and absolute neutrophil value were closely related to postoperative recurrence, and etiology was an independent predictor of tumor recurrence in patients with CS. The results of this study showed that CS caused by different etiologies showed different clinical manifestations, blood electrolyte characteristics, and that CS could affect patient cardiac structure and function. Etiology is an independent predictor of tumor recurrence in patients with CS.

Early Complications and Outcome After Treatment of Ruptured Aneurysms in Patients with Subarachnoid Hemorrhage-A Post Hoc Analysis of the EARLYDRAIN Trial.

OBJECTIVE: Aneurysmal subarachnoid hemorrhage (aSAH) from a ruptured intracranial aneurysm is a severe, life-threatening condition, with high morbidity and mortality. The current treatment often involves surgical clipping or endovascular treatment within the first 24-48 hours. Although there is ample evidence of complications in treating unruptured aneurysms, similar data in patients with acutely ruptured aneurysms are limited. The recently completed EARLYDRAIN trial showed improved neurologic results from lumbar drainage after aneurysm treatment in patients with aSAH. Using this data set, we aim to study the frequency and effects of complications and identify associated risk factors. METHODS: A substudy was carried out of the prospective multicenter randomized controlled EARLYDRAIN trial. We analyzed treatment-associated complications (bleeding and/or infarctions) detected on computed tomography on day 1 after aneurysm occlusion. Outcomes were the occurrence of postprocedural complications, secondary infarctions in the acute phase, and the modified Rankin Scale score after 6 months. RESULTS: The EARLYDRAIN trial recruited 287 patients in 19 centers. Of these patients, 56 (19.5%) experienced a treatment complication. Twenty-five patients (8.7%) experienced postprocedural intracranial hemorrhage and 34 patients (11.8%) experienced a treatment-associated infarction. Patients with a complication showed more secondary infarctions (P = 0.049) and worse neurologic outcomes after 180 days (P = 0.025) compared with patients with no complication. Aneurysm location, rebleeding before the treatment, number of patients recruited per center, and the day of the treatment were independent risk factors for the occurrence of complications. CONCLUSIONS: The present study shows that patients with aSAH frequently experience intervention-associated complications associated with aneurysm occlusion required to prevent recurrent hemorrhage. Consequently, patients with aSAH with treatment-related complications more often experience a worse clinical course and poor outcome.

Novel uses of complement inhibitors in myasthenia gravis-Two case reports.

INTRODUCTION/AIMS: Myasthenia gravis (MG) is a rare, life-threatening immune-related adverse effect (irAE) of immune checkpoint inhibitor (ICI) treatment. C5-complement inhibitors are effective treatments for acetylcholine receptor antibody (AChR ab) positive generalized MG. We describe the use of eculizumab/ravulizumab in two patients with MG receiving concomitant pembrolizumab. METHODS: This was a retrospective review of two medical records. RESULTS: Patient 1: An 80-year-old male with recurrent, non-muscle invasive transitional cell carcinoma of the bladder developed ICI-induced AChR ab positive MG (ICI-MG), myositis, and myocarditis 2 weeks after the first dose of pembrolizumab. Myositis responded to corticosteroids. MG responded to eculizumab, followed by ravulizumab. He died of metastatic cancer 8 months later. Patient 2: A 58-year-old male had refractory thymoma-associated AChR ab-positive MG, which responded to eculizumab. He developed metastatic Merkel cell cancer necessitating pembrolizumab. MG remained stable on eculizumab. He had no irAEs for 22 months, with positron emission tomographic resolution of cancer. He then developed mild, indolent retinal vasculitis, which responded to prednisone. Discontinuation of pembrolizumab for 5 months resulted in cancer recurrence; pembrolizumab was resumed with peri-infusion pulse prednisone. MG remained stable and he continues eculizumab. DISCUSSION: In the first patient, eculizumab, followed by ravulizumab, improved ICI-MG. In the second patient, eculizumab treatment may have had a prophylactic effect on the development of ICI-induced irAEs. The effect of complement inhibition on cancer outcomes of ICI therapy is unknown. A possible biologic basis for complement inhibitors in reducing irAEs of ICI, especially in the presence of underlying autoimmune disease, merits evaluation.

Allogeneic hematopoietic stem cell transplantation: A single-center experience, 2017 to 2021.

INTRODUCTION: Hematopoietic stem cell transplantation (HSCT) remains a critical treatment for advanced or high-risk hematological malignancies, posing challenges such as finding suitable donors and managing of graft-versus-host disease (GvHD). This study estimates 3-year overall survival in patients who underwent HSCT at our referral service in the state of Minas Gerais, Brazil. MATERIAL AND METHODS: This retrospective observational cohort study involved 41 patients who received HSCT between 2017 and 2021 at the Felício Rocho Hospital. Recipients received HSCT from either haploidentical donor (Haplo), matched unrelated donor (MUD), or HLA-matched sibling donor (MSD). The study evaluated parameters that included 3-year overall survival (OS), treatment-related mortality (TRM), GvHD incidence, post-transplant relapse rate, and engraftment. ANOVA, Kruskal-Wallis, and chi-square tests were used for statistical analysis. Survival curves were calculated using the Kaplan-Meier method and the Log-rank test compared the curves. RESULTS: Our study found that the engraftment time differed among groups: Haplo recipients engrafted earlier within a median of 16 days (ranging between 10 and 20 days) than MSD recipients with 18 days (ranging between 11 and 28 days), and MUD recipients with 19 days (ranging between 11 and 24 days; p = 0.019). Mild acute GvHD (grade I-II) was observed in 13 patients, progressing to chronic GvHD in 5 patients. Three-year OS rates were as follows: MSD group - 67.7%, Haplo group - 42.2%, and MUD group - 44.4% (MSD vs Haplo, p = 0.039). Three-year cumulative treatment-related mortality (TRM) rates were 17.8% for MSD group, 22.9% for Haplo group, and 22.1% for MUD group (pairwise comparisons p > 0.05). Infection-related mortality was reported in eight patients, while relapse rates at 3 years were similar across MSD, Haplo, and MUD groups (p = 0.891). Donor age influenced OS rates, showing better outcomes with donors under 45 years old, and significant differences were found in pairwise comparisons (p = 0.015). CONCLUSION: Donor type and donor age significantly impacted HSCT outcomes in our analysis, thus emphasizing the importance of rigorous donor selection in risk stratification and suggesting potential benefits for younger donors.

The absence of antibodies in longitudinally extensive transverse myelitis may predict a more favourable prognosis.

BACKGROUND: Isolated first episodes of longitudinally extensive transverse myelitis (LETM) have typically been associated with neuromyelitis optica spectrum disorder (NMOSD) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). However, in some cases, serological testing and screening for other aetiologies are negative, a condition referred to as double seronegative longitudinally extensive transverse myelitis (dsLETM). OBJECTIVE: The objective of this study was to evaluate comparative outcomes of dsLETM, MOGAD-LETM and NMOSD-LETM. METHODS: Cohort study of LETM cases seen in the UK NMOSD Highly Specialised Service between January 2008 and March 2022. RESULTS: LETM = 87 cases were identified (median onset age = 46 years (15-85); median follow-up = 46 months (1-144); 47% NMOSD-LETM = 41 (aquaporin-4 antibodies (AQP4-IgG) positive = 36), 20% MOGAD-LETM = 17 and 33% dsLETM = 29). Despite similar Expanded Disability Status Scale (EDSS) at nadir, last EDSS was higher in AQP4-IgG and seronegative NMOSD-LETM (sNMOSD) (p = 0.006). Relapses were less common in dsLETM compared to AQP4-IgG NMOSD-LETM and sNMOSD-LETM (19% vs 60% vs 100%; p = 0.001). Poor prognosis could be predicted by AQP4-IgG (odds ratio (OR) = 38.86 (95% confidence interval (CI) = 1.36-1112.86); p = 0.03) and EDSS 3 months after onset (OR = 65.85 (95% CI = 3.65-1188.60); p = 0.005). CONCLUSION: dsLETM remains clinically challenging and difficult to classify with existing nosological terminology. Despite a similar EDSS at nadir, patients with dsLETM relapsed less and had a better long-term prognosis than NMOSD-LETM.