We conducted a systematic review and meta-analysis to evaluate outcomes following chimeric antigen receptor T cell (CAR-T) therapy in relapsed/refractory acute myeloid leukemia (RR-AML).
We performed ...a literature search on PubMed, Cochrane Library, and Clinicaltrials.gov. After screening 677 manuscripts, 13 studies were included. Data was extracted following PRISMA guidelines. Pooled analysis was done using the meta-package by Schwarzer et al. Proportions with 95% confidence intervals (CI) were computed.
We analyzed 57 patients from 10 clinical trials and 3 case reports. The pooled complete and overall response rates were 49.5% (95% CI 0.18-0.81, I
=65%) and 65.2% (95% CI 0.36-0.91, I
=57%). The pooled incidence of cytokine release syndrome, immune-effector cell associated neurotoxicity syndrome, and graft-versus-host disease was estimated as 54.4% (95% CI 0.17-0.90, I
=77%), 3.9% (95% CI 0.00-0.19, I
=22%), and 1.6% (95%CI 0.00-0.21, I
=33%), respectively.
CAR-T therapy has demonstrated modest efficacy in RR-AML. Major challenges include heterogeneous disease biology, lack of a unique targetable antigen, and immune exhaustion.
Background
Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative therapy for various hematologic disorders. Alternative donor strategies such as mismatched unrelated ...donors (MMUD) offer the option of HSCT to patients lacking a human leukocyte antigen (HLA)-matched donor. We conducted a systematic review and meta-analysis to evaluate outcomes after MMUD-HSCT.
Methods
A literature search was performed on PubMed, Cochrane Library, and ClinicalTrials.gov from the inception date through April 6, 2022. After screening 2477 manuscripts, 19 studies were included. Data was extracted following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. Pooled analysis was done using the meta-package by Schwarzer et al. Proportions with 95% confidence intervals (CI) were computed.
Results
A total of 3336 patients from 19 studies were included. The median age was
52.1
years, and 53% of recipients were males. The graft source was bone marrow in 19% and peripheral blood stem cells in 81% of recipients. The median time to transplant from hematologic diagnosis was 10 (1-247) months. Hematologic diagnoses included myeloid (82.9%), lymphoid (41.1%), and other disorders (3%). The reduced intensity and myeloablative conditioning were used in 65.6% and 32% of recipients, respectively.
In-vivo
T-cell depletion was performed in 56.7% of the patients. Most patients had one (87.9%) or two (11.4%) antigen HLA-mismatch. The pooled 1-year overall survival (OS) was 63.9% (95% CI 0.57-0.71, n=1426/2706), and the pooled 3-year OS was 42.1% (95% CI 0.34.2-0.50, n=907/2355). The pooled progression-free survival was 46.6% (95% CI 0.39-0.55, n=1295/3253) after a median follow-up of 1.8 (range 1-6) years. The pooled relapse rate was 26.8% (95% CI 0.22-0.32, n=972/3253) after a median follow-up of 2.25 (1-3) years. The pooled incidence of acute (grade II-IV) graft-versus-host disease (GVHD) and chronic GVHD was 36.4% (95% CI 0.31-0.42, n=1131/3030) and 41.2% (95% CI 0.35-0.48, n=1337/3228), respectively. The pooled non-relapse mortality was 22.6% (95% CI 0.17-0.29, n=888/3196) after a median follow-up of 2.6 (1-5) years.
Conclusion
MMUD-HSCT has demonstrated favorable outcomes with an acceptable toxicity profile. It represents a promising option in patients lacking an HLA-matched or haploidentical donor and may expand HSCT access to underrepresented racial and ethnic populations.
Heatstroke, defined as an elevated core body temperature above 40°C accompanied by altered mental status (e.g., confusion, disorientation, seizure and coma), is the most severe and life-threatening ...condition in the spectrum of heat-related illnesses. Heatstroke patients may present with multi-organ dysfunction, but with rapid cooling and organ failure management, a full recovery often occurs within weeks. Long-term impairment is rare, with neurological impairment occurring most frequently. Despite an abundance of research on the persistent neurological and hepatic impairments, our knowledge of the long-term cardiovascular events in patients with heatstroke history is poor. We wondered whether heatstroke leads to cardiovascular diseases long after full recovery. Using Pubmed, Web of Science and Scopus, we gathered cohort studies looking at cardiovascular disease incidence or mortality as an outcome, including heatstroke animal studies. Based on the available literature, we found that a history of heatstroke is associated with an increased risk of cardiovascular diseases, including ischemic heart disease, heart failure and atrial fibrillation. Delayed metabolic disturbances occurring in exertional heatstroke mice are linked to the formation of atherosclerosis and the development of heart failure. These processes provide potential pathophysiological pathways leading to ischemic heart disease and heart failure in heatstroke patients. Our findings may massively impact our understanding of heatstroke recovery and the follow up of heatstroke patients. Therefore larger, more adequately powered cohort studies with cardiovascular disease as an outcome, in tandem with animal studies examining the underlying pathophysiology, are required to confirm or reject these findings and answer the proposed questions.
Lactococcus garvieae is a part of the genus Lactococcus which was previously a part of the genus Streptococcus. It has been associated with serious diseases in aquaculture. However, human infections ...are rare. The most common presentation in humans is infective endocarditis. Urinary tract infection (UTI) is a unique presentation of this pathogen.We report the case of a 70-year-old male with a past history of benign prostatic hyperplasia who presented with confusion. Urinalysis confirmed the growth of L. garvieae. A seven-day treatment course of amoxicillin-clavulanate successfully treated the patient.The risk factors for acquiring the L. garvieae infections include contact with seafood or aquaculture. Other risk factors include immunosuppression, gastric acid suppression, and anatomical or physiological defect in the gastrointestinal tract. Special tests, such as VITEK® 2, API® 32 strep system, 16S rRNA, or polymerase chain reaction (PCR) testing, are needed for its diagnosis. Hence, we suggest underreporting of the infection may be possible.It is a novel cause of UTI, we suggest a high index of suspicion should be kept, especially in people with associated risk factors or exposure to seafood.
Nocardia is an uncommon gram-positive, weakly acid-fast bacterium that causes systemic or localized suppurative disease in humans and animals. Nocardiosis is typically regarded as an opportunistic ...infection, but approximately one-third of the patients are immunocompetent. The most common presentation is pulmonary disease (39%) followed by systemic involvement, defined as involvement of more than two sites; cutaneous presentation constitutes only 8% of the cases. Nocardia is widely distributed geographically; however, in the US, it is mostly found in warm and dry areas of South West and South East.We present a perfect case of cutaneous nocardiosis of a 70-year-old male, who presented with a traumatic splinter injury, leading to pustules formation on the right index finger, along with erythema and induration of the right arm. The patient was empirically diagnosed and treated for cellulitis, with amoxicillin and clavulanic acid, resulting in deterioration of the wound. The patient underwent incision and drainage and wound culture grew nocardia.The index of suspicion should be kept in mind while treating infectious blisters which have failed outpatient cellulitis treatment, immunocompromised hosts, and in nocardia prevalent regions.
A sexual headache or coital cephalgia is a headache associated with sexual activity and is a well-recognised condition. It is usually benign, primary and self-limiting. However, occasionally sexual ...headaches can result from more sinister causes. Intraparenchymal and subdural haemorrhages have been reported as secondary causes of sexual headaches. We present the case of a 61-year-old woman with no comorbidities who presented acutely with a sexual headache and vision loss, and was found to have an occipital and parietal intraparenchymal haemorrhage. She was normotensive and after extensive workup was found to have no predisposing condition for her haemorrhage. The patient had an uneventful recovery with physical rehabilitation and had regular follow-ups, with no residual weakness. She was in a completely normal state of health 1 year after her event, and continued to be off any medications.
IntroductionDilated cardiomyopathy has been associated with remarkably high mortality despite guideline-directed therapy. This study compares the all-cause mortality rate between a cardiac ...contractility modulation group and a standard therapy group in patients with dilated cardiomyopathy who were monitored via follow-up for 12 weeks or more.Materials and methodsWe conducted a systematic search of Medline (PubMed) and Cochrane Central Register of Controlled Trials for abstracts and fully published studies (from inception to October 2018). We searched for articles comparing cardiac contractility modulation device therapy with standard therapy for patients with dilated cardiomyopathy between September 1, 2018, and October 30, 2018.Only fully published randomized clinical trials comparing all-cause mortality outcomes of device therapy and standard therapy for patients with dilated cardiomyopathy were included in our meta-analysis. A total of 673 studies were identified. Studies that were systematic reviews or meta-analyses, study designs or protocols, trials on other regimens, wherein medical therapy was not compared, or wherein the primary outcome of mortality was not assessed, were excluded.Data were abstracted by two independent reviewers. A random-effect model using the Mantel-Haenszel method calculated the weighted risk ratio (RR). Statistical analyses were performed using Review Manager 5.3 (The Nordic Cochrane Centre, The Cochrane Collaboration; Copenhagen). The primary outcome of interest was a comparison of all-cause mortality between the two groups when patients were monitored via follow-up for 12 weeks or more.ResultsFour fully published randomized clinical trials met the inclusion criteria of our analysis. A random-effect model using the Mantel-Haenszel method calculated the weighted RR. Our analysis included a total of 930 patients. The cardiac contractility modulation therapy group showed no significant reduction in all-cause mortality compared to the standard therapy group (RR, 0.63; 95% CI, 0.29-1.35; P = .23). However, the trend was toward device therapy. Tests for statistical heterogeneity did not show any significant heterogeneity (P = .82, I2 = 0%).ConclusionsCardiac contractility modulation device therapy is not associated with significant all-cause mortality reduction in patients with dilated cardiomyopathy. Our meta-analysis underscores the need for a large randomized controlled trial on the efficacy of cardiac contractility modulation in a population with dilated cardiomyopathy who are ineligible for cardiac resynchronization therapy.
Burkitt lymphoma (BL) is a highly aggressive non-Hodgkin B-cell lymphoma characterized by the translocation and deregulation of the MYC (MyeloCytomatosis) gene on chromosome 8. Three distinct ...clinical forms of BL are recognized: endemic (African), sporadic (non-endemic), and immunodeficiency-associated. Bilateral renal infiltration leading to acute kidney injury (AKI) is a rare initial presentation of BL. Diagnosis is usually made after evaluating the histology and immunophenotyping of the affected tissue.We report a case of a 46-year-old male who presented with symptoms of AKI resulting from infiltrative disease, a primary presentation of lymphoma. The patient was a known case of systemic lupus erythematosus (SLE) for the last five years and was referred to the nephrology department due to acute elevation in creatinine, from 0.8 mg/dL to 3.57 mg/dL. On physical examination, there was no lymphadenopathy. Nephrology and SLE workup revealed low complement protein levels and absolute neutrophils, lymphocytes, and metamyelocytes. Renal ultrasound (USG) showed both kidneys with symmetric and edematous appearance. Biopsy affirmed high-grade B-cell lymphoma, positive for BCL-6 (B-cell leukemia/lymphoma) and CD-10 (cell surface marker) and negative for BCL-2 (B-cell leukemia/lymphoma). PET (positron emission tomography) scan showed extensive hypermetabolic lymphadenopathy in multiple areas. The patient was started on chemotherapy and on continuous renal replacement therapy. He improved clinically, and his creatinine lowered down to 0.8 mg/dL. Repeat USG showed decreased edematous appearance of both kidneys.Primary renal infiltration by BL is a rare presentation in adults. Prompt renal biopsy will change the course of treatment and can affect the prognosis. It is thoroughly advised to keep this malignancy in mind when making a diagnosis for AKI.
Rheumatoid vasculitis (RV) is an infrequent complication of longstanding severe rheumatoid arthritis (RA). The active vasculitis associated with rheumatoid disease occurs in about 1%-5% of the ...patient population. RV is a manifestation of “extra-articular” rheumatoid arthritis and involves the small- and medium-sized arteries in the body. Newer RA treatments, including biologic therapies, offer a broader array of potential therapeutic options, although no controlled trials exist to guide treatment. In general, following tissue confirmation of the diagnosis, the severity of organ involvement and disease manifestations can guide treatment decisions. We want to alert clinicians of this unique yet severe complication of RA which has high morbidity and mortality. We describe a thought-provoking case of a 44-year-old male with past medical history (PMH) of hypertension who presented with over three-month history of lower extremity (LE) swelling, discoloration, and ulceration. Arthralgias with constitutional symptoms (fatigue, weight loss), large pericardial effusion, was found to have leukocytoclastic vasculitis along with rheumatoid factor (RF) >650, and anti-cyclic citrullinated peptide (anti-CCP) antibodies >300, low C4 and normal C3. Pericardial fluid appeared serous, exudative, showed histiocytes, multinucleated giant cells and necrotic debris consistent with rheumatoid effusion. Skin, right shin, punch biopsy showed epidermal necrosis from underlying occlusive vasculopathy. Skin, left lower back, punch biopsy showed focal leukocytoclastic vasculitis. The patient was started on high dose steroids with marked improvement in the symptoms, Rituximab was planned awaiting QuantiFERON to be negative. Pan-CT angiography of the whole body was negative for any vascular changes ruling out polyarteritis nodosa (PAN).
Brucellosis is a zoonotic disease, caused by a Gram-negative coccobacillus of Brucella genus, transmitted to humans by animals, especially cattle. It rarely involves the nervous system ...(neurobrucellosis); only a few cases present with hearing loss. We report a case of neurobrucellosis, that presented with bilateral sensorineural hearing loss and mild to moderate persistent headache. To the best of our knowledge, this is the first well-documented case from Nepal.
The patient was a 40-year-old Asian male shepherd from the western mountainous region of Nepal who came to the emergency department of Manipal Teaching Hospital, Pokhara in May, 2018 and did a follow-up for 6 months. He presented with high-grade fever, profuse sweating, headache, myalgia, and bilateral sensorineural hearing loss. His history of consuming raw milk of cattle, symptoms including persistent mild to moderate headache, bilateral hearing loss, and serological findings were suggestive of neurobrucellosis. Following treatment, the symptoms improved, including the complete recovery of hearing loss.
Hearing loss may be the manifestation of neurobrucellosis. Physicians should know about such presentations in brucella endemic areas.
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