Survival analysis in nonagenarian patients with non-hip lower limb fractures.

BACKGROUND: The United Kingdom has an aging population with nearly 1 in 5 being over the age of 65, and over 0.5 million over the age of 90. The treatment of acute fractures of the lower limb in the nonagenarian cohort of patients poses a technical challenge to orthopaedic surgeons. AIM: To report the fracture incidence, survival outcomes of treating acute non-hip lower limb fractures in nonagenarians in Major Trauma Centre. METHODS: Thirty Lower limb long bone fractures in patients of age from 90 to 99 years were identified during 12-mo at a Level 1 trauma centre from a computerized database. A retrospective evaluation performed for fracture incidence, treatment, length of hospital duration and mortality at 30-d, 1-year and 2-year. RESULTS: Thirty fractures (28 patients) were identified, twenty-four fractures were treated with surgery (mean age 93 years SD ± 2.59) and 6 managed conservatively (mean age 94 years SD ± 2.07). The mean length of the hospital stay was 18.2 d for both groups. The 30-d, 1-year and 2-year mortality risks were 1/23, 6/23 and 9/23 (4%, 26% and 39%) in the surgery group and 0/5, 1/5 and 2/5 (0%, 20% and 40%) in the conservative group, with no evidence for a difference between the two groups at any time point. CONCLUSION: Nonagenarians in the surgical group had similar length of hospital stay and mortality risks as those treated conservatively. Patients with fewer comorbidities and admitted from their own home were offered surgery.

Subtalar dislocations: Mechanisms, clinical presentation and methods of reduction.

Subtalar joint is a complex joint in hindfoot formed by the talus superiorly and the calcaneus and navicular inferiorly. Subtalar dislocations are high-mechanism injuries, which are caused by simultaneous dislocation of both talonavicular and talocalcaneal joints, without major fracture of the talus. They are usually classified as medial (most common), lateral, anterior and posterior dislocations, based on the position of foot in relation to talus and the indirect forces that have been applied to cause this significant injury. They are usually diagnosed by X rays, but computed tomography and magnetic resonance imaging can be used to identify associated intra-articular fractures and peri-talar soft tissue injuries respectively. Majority being closed injuries, can be managed in ED by closed reduction and cast immobilisation, but if they are open, have poor outcomes. Complications that ensue open dislocations are post-traumatic arthritis, instability and avascular necrosis.

Massive Hemoptysis in Previously Treated Pulmonary Tuberculosis: A Case Series.

Hemoptysis in tuberculosis (TB) is associated with parenchymal distortion and vascular complications linked to prior pulmonary TB. Massive hemoptysis is defined as the expectoration of large volumes of blood. Massive hemoptysis can lead to high morbidity and mortality rates due to hemodynamic instability and airway compromise. In this case series, we present two cases with massive hemoptysis caused by the rupture of the bronchial artery, which achieved hemostasis after fluoroscopy-guided arterial embolization. This series highlights the multiple etiologies of hemoptysis in patients with post-pulmonary TB destruction and the need for various diagnostic and therapeutic modalities. Hemoptysis in patients with prior pulmonary TB can be massive and life-threatening. Timely diagnosis, accurate modality to isolate the source, and appropriate intervention could potentially prevent further lethal complications.

Top 100 Cited Articles on Clinical Hematopoietic Stem Cell Transplantation: A Bibliometric Analysis.

We conducted a bibliometric analysis to identify scholarly impact and factors associated with the top 100 cited articles on clinical hematopoietic stem cell transplantation (HSCT). In January 2021, a title-specific search was conducted. Non-HSCT and pre-clinical (in-vitro and animal) studies were excluded. A total of 39,406 records were identified and a list of the top 100 articles was made. Articles included in our study were characterized by the citations received, publication year, topic, study design, authors, h-index, and institutions. Linear regression analyses were performed. The 100 most cited articles were published over 52 years from 1968 to 2020, with a maximum number of articles (n = 40) published in the 1990s decade. Top-100 articles were cited 62,002 times with a median citation count of 465 (range 336-2240). The top-cited articles originated from 12 countries. United States contributed 69 articles. The University of Washington Fred Hutchinson Cancer Center (n = 15) was the leading institution. Blood (n = 32) and New England Journal of Medicine (n = 31) made the greatest contribution, and 52 manuscripts were clinical trials. The first author's H-index significantly correlated with citation count while journal impact factor, years since publication, first author's gender, and the number of authors did not have a significant association with the number of citations. In a multivariate regression model, the first author's h-index (regression coefficient 5.46, 95% confidence interval 2.99 to 7.93, p < 0.001) independently correlated with the citation count. Our study highlights the most influential articles on clinical HSCT and provides valuable insight for future research needs of the specialty.

Gender disparities in the National Institutes of Health funding for hematologic malignancies and cellular therapies.

We investigated gender inequality in the National Institutes of Health (NIH) funding for hematologic malignancies and cellular therapies (HMCT). The data were retrieved from the NIH Research Portfolio Online Reporting Tools (RePORT). In 2018-2019, 1834 grants totaling $799 million were awarded (men 71% vs. women 29%) to 975 principal investigators (PIs), including 680 (70%) male PIs and 295 (30%) female PIs. There was no significant gender difference in the mean grant amount per PI. Male PIs as compared to female PIs had a higher h-index (44 vs 31, p < 0.001), a higher number of publications (159.5 vs 94, p < 0.001), and higher years of active research (26 vs 21, p < 0.001). In multivariate analyses, a higher h-index independently predicted a higher mean grant amount per PI (p = 0.010), and female PIs were independently less likely to have a higher h-index (p < 0.001). Our study shows significant gender disparity in the NIH funding for HMCT research.

Liver transplantation during global COVID-19 pandemic.

The coronavirus disease 2019 (COVID-19) caused by severe acute respiratory disease respiratory syndrome coronavirus-2 has significantly impacted the health care systems globally. Liver transplantation (LT) has faced an unequivocal challenge during this unprecedented time. This targeted review aims to cover most of the clinical issues, challenges and concerns about LT during the COVID-19 pandemic and discuss the most updated literature on this rapidly emerging subject.

Current systematic reviews and meta-analyses of COVID-19.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has left a significant impact on the world's health, economic and political systems; as of November 20, 2020, more than 57 million people have been infected worldwide, with over 1.3 million deaths. While the global spotlight is currently focused on combating this pandemic through means ranging from finding a treatment among existing therapeutic agents to inventing a vaccine that can aid in halting the further loss of life. AIM: To collect all systematic reviews and meta-analyses published related to COVID-19 to better identify available evidence, highlight gaps in knowledge, and elucidate further meta-analyses and umbrella reviews that are yet to be performed. METHODS: We explored studies based on systematic reviews and meta-analyses with the key-terms, including severe acute respiratory syndrome (SARS), SARS virus, coronavirus disease, COVID-19, and SARS coronavirus-2. The included studies were extracted from Embase, Medline, and Cochrane databases. The publication timeframe of included studies ranged between January 01, 2020, to October 30, 2020. Studies that were published in languages other than English were not considered for this systematic review. The finalized full-text articles are freely accessible in the public domain. RESULTS: Searching Embase, Medline, and Cochrane databases resulted in 1906, 669, and 19 results, respectively, that comprised 2594 studies. 515 duplicates were subsequently removed, leaving 2079 studies. The inclusion criteria were systematic reviews or meta-analyses. 860 results were excluded for being a review article, scope review, rapid review, panel review, or guideline that produced a total of 1219 studies. After screening articles were categorized, the included articles were put into main groups of clinical presentation, epidemiology, screening and diagnosis, severity assessment, special populations, and treatment. Subsequently, there was a second subclassification into the following groups: gastrointestinal, cardiovascular, neurological, stroke, thrombosis, anosmia and dysgeusia, ocular manifestations, nephrology, cutaneous manifestations, D-dimer, lymphocyte, anticoagulation, antivirals, convalescent plasma, immunosuppressants, corticosteroids, hydroxychloroquine, renin-angiotensin-aldosterone system, technology, diabetes mellitus, obesity, pregnancy, children, mental health, smoking, cancer, and transplant. CONCLUSION: Among the included articles, it is clear that further research is needed regarding treatment options and vaccines. With more studies, data will be less heterogeneous, and statistical analysis can be better applied to provide more robust clinical evidence. This study was not designed to give recommendations regarding the management of COVID-19.

Management of Relapsed Hairy Cell Leukemia: A Systematic Review of Novel Agents and Targeted Therapies.

BACKGROUND: Hairy cell leukemia (HCL) responds well to purine analogs with an overall median relapse free survival of 11-16 years. Most patients can be retreated with the same or a different purine analog however a subset of patients will become resistant or develop cumulative toxicities. Novel agents such as Vemurafenib (BRAF kinase inhibitor), Bendamustine/Rituximab (BR), Moxetumomab pasudotox (anti CD-22 recombinant immunotoxin) and Ibrutinib have emerging roles in patients with relapsed HCL. METHODS: Five databases (PubMed, Embase, Cochrane Library, Web of Science and ClinicalTrials.gov) were searched using the following search terms: "hairy cell leukemia" or "leukemia, hairy cell" AND "relapse" or "recurrence". We included only prospective clinical trials with outcome data. RESULTS: Vemurafenib monotherapy was evaluated in two separate arms of a phase 2 trial. In the US arm (n=24), the ORR was 100% (CR 42%; PR 58%). In the Italian arm (n=26), the ORR was 96% (CR 35%; PR 62%). In a phase 2 study (n=25), the combination of vemurafenib and rituximab showed CR of 100%. The combination of BR achieved an ORR of 100% whereas CR was 50% and 67% at a bendamustine dose of 70mg/m2 (n=6) and 90 mg/m2 (n=6) respectively. In a phase 3 trial, moxetumomab pasudotox (n=80) had an ORR of 75% (CR 41%). Single agent Ibrutinib (n=37) had an ORR of 54%. Therapies were generally well tolerated. CONCLUSION: Novel agents have good efficacy in HCL in patients with multiple relapses.

Diffuse Large B-Cell Lymphoma of the Left Upper Extremity Mimicking a Sarcoma.

Diffuse large B-cell lymphoma (DLBCL) can arise in both lymph nodes and extranodal sites. DLBCLs rarely present in the soft tissue of the upper extremity. We report a case of a 64-year-old woman who presented with a large left upper arm mass and underwent surgical resection under the presumptive diagnosis of sarcoma but the final pathology showed DLBCL. Sarcomas are common malignant tumors of the soft tissue of the extremities, but lymphomas also occasionally present as a soft tissue mass. It is important to keep lymphomas in mind in order to avoid unnecessary surgical excisions.

Outcomes with CD34-Selected Stem Cell Boost for Poor Graft Function after Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.

Poor graft function (PGF) is a life-threatening complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) characterized by multilineage cytopenia in the absence of mixed donor chimerism (<95% donor), relapse, or severe graft-versus-host disease (GVHD). We present a systemic review and meta-analysis aimed at assessing the outcomes with CD34-selected stem cell boost (SCB) for PGF in adult allo-HSCT recipients. We screened a total of 1753 records identified from 4 databases (PubMed, Embase, Cochrane, and ClinicalTrials.gov) following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, using the search terms "hematological malignancies," "hematopoietic stem cell transplantation," "CD34 antigen(s)," "graft failure," and "poor graft function," from the date of inception to January 2021. After excluding review, duplicate, and nonrelevant articles, we included 7 studies reporting outcomes following administration of CD34-selected SCB for PGF after allo-HSCT, including hematologic complete response (CR) and overall response rate (ORR), GVHD, and overall survival (OS). Quality evaluation was done using the National Institutes of Health quality assessment tool. Pooled analysis was done using the R 'meta' package, and proportions with 95% confidence intervals (CIs) were computed. The inter-study variance was calculated using the Der Simonian-Laird estimator. We identified 209 patients who received CD34-selected SCB for PGF after allo-HSCT. The median age was 49 years (range, 18 to 69 years), and 61% were men. Primary graft sources included peripheral blood stem cells (72%) and bone marrow (28%). Donor types were matched sibling (37%), matched unrelated (36%), mismatched unrelated (22%), and haploidentical donors (5%). The median time from allo-HSCT to SCB was 138 days (range, 113 to 450 days). The median SCB dose was 3.45 × 106 CD34 cells/kg (range, 3.1 to 4.9 × 106 cells/kg). CR and ORR were 72% (95% CI, 63% to 79%; I2 = 26%) and 80% (95% CI, 74% to 85%; I2 = 0%), respectively. After a median follow-up of 42 months (range, 30 to 77 months), the actuarial survival rate was 54% (95% CI, 47% to 61%; I2 = 0%). OS ranged from 80% at 1 year to 40% at 9 years. The incidences of acute and chronic GVHD after SCB were 17% (95% CI, 13% to 23%; I2 = 0%) and 18% (95% CI, 8% to 34%; I2 = 76%), respectively. Nonrelapse mortality was reported in 42 patients, with a pooled rate of 27% (95% CI, 17% to 40; I2 = 59%), and death due to relapse was reported in 25 patients, with a pooled rate of 17% (95% CI, 11% to 23%; I2 = 0%). Our data show that CD34-selected SCB improves outcomes after PGF post allo-HSCT with an acceptable toxicity profile. The literature lacks high-quality randomized evidence, and there remains an unmet need for prospective studies to address the optimal dosing and manipulation of SCB. © 2021 American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc.

A Rare Case of Small Cell Lung Cancer With an Epidermal Growth Factor Receptor Mutation and Its Response to Osimertinib.

Small cell lung cancer (SCLC) accounts for less than 15% of the cases of lung cancer. Epidermal growth factor receptor (EGFR) mutations are rarely reported in association with SCLC. EGFR tyrosine kinase inhibitors (TKI) are approved as the first-line therapy for metastatic non-small cell lung cancer (NSCLC). The clinical effect of EGFR mutations and its response to osimertinib are unknown in SCLC. We report a case of EGFR-positive metastatic SCLC in a 63-year-old female who was treated with the third-generation TKI, osimertinib.

Atypical Carcinoid Tumor of the Mediastinum Presenting as Cushing's Syndrome in an Otherwise Healthy Young Male.

Primary neuroendocrine tumors (NETs) are rare types of malignancies that can have a variety of presentations due to the ubiquitous distribution of neuroendocrine cells within the body. While mediastinal masses are not uncommon, NETs arising from the anterior mediastinum are rare and often originate from the thymus gland. A subset of NETs, atypical carcinoids, are more commonly seen in the lungs or gastrointestinal organs and often present with endocrine syndromes, chiefly Cushing's syndrome. The behavior of atypical carcinoid tumors within the mediastinum is often aggressive and clinical presentations vary widely. In this report, we describe a case of an atypical carcinoid tumor within the anterior mediastinum in an otherwise healthy young male with signs and symptoms of Cushing's syndrome.

Further evidence for the benefit of therapeutic plasma exchange for acute multi-organ failure syndrome refractory to red cell exchange in sickle cell disease.

Acute multiorgan failure syndrome (MOFS) remains a significant cause of mortality in sickle cell disease (SCD) patients despite red cell exchange (RCE). In small case series and reports, therapeutic plasma exchange (TPE) has shown benefit in MOFS. As further support for consideration of this modality, we present two patients with SCD and MOFS refractory to RCE who were subsequently treated with TPE. Fresh frozen plasma was used as the replacement fluid. Despite estimated hospital mortality of 40% at the time of intensive care unit admission, both patients showed marked clinical improvement with TPE treatment. Our cases add to the evidence supporting the potential inclusion of MOFS secondary to acute SCD as an indication for TPE in the next edition of the American Society of Apheresis Guidelines on the Use of Therapeutic Apheresis in Clinical Practice.

A Systematic Review of the Role of Chimeric Antigen Receptor T (CAR-T) Cell Therapy in the Treatment of Solid Tumors.

Chimeric antigen receptor T (CAR-T) cell therapy utilizes patients' own T lymphocytes that are engineered to attack cancer cells. It is Food and Drug Administration (FDA)-approved in various hematological malignancies and currently being evaluated in solid cancers in early phase studies. We did a systematic review consisting of 15 prospective clinical trials (n=159) evaluating CAR-T cells in solid cancers. Early phase trials showed promising response rates in ovarian epithelial cancer (100%), human epidermal growth factor receptor 2 (HER2)-positive sarcoma (67%), epidermal growth factor receptor (EGFR)-positive biliary tract cancer (65%), advanced gastric/pancreatic cancer (82%), hepatocellular carcinoma (67%), and colorectal cancer (70%). The median overall response across all malignancies was 62% (range 17%-100%). Median progression-free survival and overall survival were not reached in most trials. Cytokine release syndrome was seen in only one patient with cholangiocarcinoma who received EGFR-specific CAR-T cell therapy. Although survival data is still not mature, CAR-T cell therapy in solid malignancies did show encouraging response rates and was well-tolerated.

A Case of Rapidly Proliferative Glomerulonephritis Secondary to Syphilis That Responded to Treatment With Penicillin.

The involvement of kidneys in syphilis has been reported in the literature with the majority of cases presenting with nephrotic-range proteinuria. We report a case of rapidly proliferative glomerulonephritis in a patient with secondary syphilis. A 40-year-old male with a history of human immunodeficiency virus (HIV), chronic hepatitis B virus, and chronic kidney disease stage 2 presented with fatigue, anorexia, weight loss, arthralgia, chills, and rash throughout the body. The patient was non-compliant with HIV medication and had unprotected sexual intercourse. Labs showed blood urea nitrogen of 57 mg/dL (range: 7-23 mg/dL), creatinine 8.2 mg/dL (range: 0.5-1.3 mg/dL), and high titers of rapid plasma reagin. The biopsy showed crescentic glomerulonephritis with c3 deposition in mesangium and basement membrane. The patient responded to treatment with penicillin therapy with gradual improvement in kidney function.

Hemophagocytic Lymphohistiocytosis as the Presenting Manifestation of Relapsed Classic Hodgkin's Lymphoma in the Presence of Concurrent Human Immunodeficiency Virus, Genital Herpes, Epstein-Barr Virus and Mycobacterium Avium Complex Infection.

Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening disorder of uncontrolled immune activation which is usually divided into two main types. Primary, which is associated with genetic mutation and familial predisposition and secondary, which is usually associated with infections, malignancies and autoimmune conditions. More often multiple risk factors are present at the time of initial presentation. We report a case where HLH was the presenting manifestation of relapsed Classic Hodgkin's Lymphoma in the presence of multiple risk factors of secondary HLH such as human immunodeficiency virus (HIV), active genital herpes, Epstein-Barr virus (EBV) viremia, Mycobacterium avium complex (MAC) infection and prior chemotherapy. A 38-year-old male to female transgender woman presented with one-week history of fever, nausea, vomiting and generalized weakness. The past medical history was significant for HIV and previously treated and positron emission tomography (PET) scan confirmed complete remission of Classic Hodgkin's Lymphoma. Physical examination showed BP 92/40 mmHg, fever of 102.6 F, heart rate of 114 beats per minutes, diffuse abdominal tenderness and male genitalia with multiple small ulcerative lesions. Labs showed pancytopenia, hyponatremia, mildly elevated total and direct bilirubin, transaminitis, CD-4 count 96/mcL, HIV viral load undetectable and COVID-19 polymerase chain reaction (PCR) negative. Imaging showed right middle lung lobe consolidation and hepatosplenomegaly with multiple hypodense lesions. Lymphadenopathy was reported in mediastinum and retroperitoneum. The patient was initially treated with broad spectrum antibiotics, IV fluids, vasopressors and stress dose steroids. After initial improvement, vasopressors and steroids were stopped. The patient again started spiking fever on day 9 despite being on antibiotics. Workup showed EBV viremia, genital herpes and evidence of MAC infection on sputum culture. No improvement noted despite appropriate treatment for genital herpes and MAC. Additional lab work showed hyperferritinemia and elevated soluble Interleukin-2 receptors. The patient was diagnosed with HLH as per HLH-2004 criteria and treated with dexamethasone and etoposide. Bone marrow biopsy confirmed hemophagocytosis and immunoperoxidase staining established the diagnosis of relapsed Classic Hodgkin's Lymphoma. We can conclude that in patients with a history of hematological malignancy presenting with HLH, a high degree of suspicion for relapse should be maintained even in the presence of other risk factors.

Cauda equina compression in metastatic prostate cancer.

A 67-year-old man presented to his general practitioner with intermittent episodes of unilateral sciatica over a 2-month period for which he was referred for an outpatient MRI of his spine. This evidenced a significant lumbar vertebral mass that showed tight canal stenosis and compression of the cauda equina. The patient was sent to the emergency department for management by orthopaedic surgeons. He was mobilising independently, pain free on arrival and without neurological deficit on assessment. Clinically, this patient presented with no red flag symptoms of cauda equina syndrome or reason to suspect malignancy. In these circumstances, National Institute for Health and Care Excellence guidelines do not support radiological investigation of the spine outside of specialist services. However, in this case, investigation helped deliver urgent care for cancer that otherwise may have been delayed. This leads to the question, do the current guidelines meet clinical requirements?

Onset of Ketosis-Prone Diabetes in the Setting of COVID-19 Infection.

Diabetic ketoacidosis is typically associated with type I diabetes mellitus, but it can be associated with type II diabetes mellitus under the conditions of extreme stress or as a presenting manifestation of ketosis-prone type II diabetes mellitus. A 38-year-old prediabetic male presented to the emergency room with hyperglycemia six weeks after recovery from coronavirus disease 2019 (COVID-19) pneumonia. Laboratory results showed severe hyperglycemia, metabolic acidosis, positive ketones in urine and blood, and elevated fasting C- peptide level. COVID-19 polymerase chain reaction (PCR) was negative, and immunoglobulin G (IgG) antibodies were positive. The workup was completely unremarkable for acute infection. Hemoglobin A1C increased from 6.1% to 10.8% within six weeks. The mechanism by which COVID-19 infection may trigger the onset of full-blown diabetes mellitus remains unknown. Viral infection may cause the direct destruction of pancreatic beta cells or trigger the changes in the body that induce the state of insulin resistance. Antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection may cross-react or interfere with the functioning of endogenous insulin. The association between type II diabetes and COVID-19 infections needs additional investigations to ascertain the exact mechanism by which COVID-19 infection triggers the onset of full-blown diabetes mellitus.

Thrombocytopenia Secondary to Herpes Simplex Virus-2 Infection Successfully Treated by Acyclovir.

Thrombocytopenia is a common clinical condition associated with a wide variety of clinical conditions including infections, malignancy, medications, liver disorder, and autoimmune conditions, etc. The association between thrombocytopenia and herpes simplex virus (HSV) is reported only once in a case report dating back to 1978. We report a case of a 66-year-old female with generalized weakness, mechanical fall, genital ulcerations, and breast fold and genital area skin redness, warmth, and mild tenderness. Initial labs showed mild leukocytosis, normal platelet count, mild lactic acidosis, and urine analysis suggestive of urinary tract infection. The patient was started on broad-spectrum antibiotics. During the course of hospitalization, the patient developed severe thrombocytopenia with platelet counts dropping less than 40000/µL (normal range: 150,000-450,000/µL), and genital pain and ulceration worsened. The genital swab was sent which came back positive for the HSV-2 virus. Soon after the start of acyclovir for HSV-2 infection, the genital pain and ulceration improved and platelet counts gradually increased to 157,000/µL. Other causes of thrombocytopenia such as sepsis, heparin-induced thrombocytopenia, consumptive coagulopathy, medication-induced thrombocytopenia, immune thrombocytopenia, and thrombotic thrombocytopenic purpura were ruled out.