ABSTRACT
Rituximab-based chemo-immunotherapy is currently the standard first-line treatment for Waldenstrom macroglobulinaemia (WM), while ibrutinib has emerged as an alternative. In the absence of randomised trials (RCTs) comparing these regimens, the optimal first-line treatment for WM remains uncertain. In this systematic review and meta-analysis, we sought to assess the efficacy and safety of first-line treatment regimens for WM. We searched key databases from January 2007 to March 2023, including phase II and III trials, including treatment-naïve WM patients treated with rituximab-based regimens or ibrutinib. Response rates, progression-free survival (PFS), overall survival (OS), and toxicities were evaluated. Four phase III and seven phase II trials were included among 736 unique records. Pooled response rates from all comparative and non-comparative trials were 46%, 33% and 26% for bendamustine rituximab (BR), bortezomib-dexamethasone, cyclophosphamide, rituximab (BDRC) and ibrutinib rituximab (IR), respectively. Two-year pooled PFS was 89%, 81% and 82% with BR, BDRC and IR, respectively. Neuropathy was more frequent with bortezomib, while haematologic and cardiac toxicities were more common with chemo-immunotherapy and ibrutinib-based regimens respectively. Our findings suggest that BR yields higher response rates than bortezomib or ibrutinib-based combinations. RCTs comparing BR against emerging therapies, including novel Bruton Tyrosine Kinase Inhibitors, are warranted.
Subject(s)
Waldenstrom Macroglobulinemia , Humans , Waldenstrom Macroglobulinemia/drug therapy , Rituximab/adverse effects , Bortezomib , Clinical Protocols , CyclophosphamideABSTRACT
BACKGROUND: Arterial and venous thrombosis are reported to be common in critically ill COVID-19 patients. METHOD AND RESULTS: This is a national multicenter retrospective observational study involving all consecutive adult COVID-19 patients who required intensive care units (ICU) admission between 23 January 2020 and 30 April 2020 in Singapore. One hundred eleven patients were included and the venous and arterial thrombotic rates in ICU were 1.8% (n = 2) and 9.9% (n = 11), respectively. Major bleeding rate was 14.8% (n = 16). CONCLUSIONS: Critically ill COVID-19 patients in Singapore have lower venous thromboembolism but higher arterial thrombosis rates and bleeding manifestations than other reported cohorts.
Subject(s)
Anemia/etiology , Betacoronavirus , Blood Transfusion/statistics & numerical data , Coronavirus Infections/therapy , Pneumonia, Viral/therapy , Acute Kidney Injury/etiology , Adult , Aged , Anemia/therapy , Blood Banks/statistics & numerical data , COVID-19 , Cardiovascular Diseases/complications , Coronavirus Infections/complications , Coronavirus Infections/epidemiology , Fatal Outcome , Female , Gastrointestinal Diseases/complications , Gastrointestinal Hemorrhage/complications , Humans , Male , Middle Aged , Multiple Organ Failure/etiology , Pandemics , Plasma , Pneumonia, Viral/complications , Pneumonia, Viral/epidemiology , Procedures and Techniques Utilization , Respiratory Distress Syndrome/etiology , SARS-CoV-2 , Shock, Septic/complications , SingaporeSubject(s)
Betacoronavirus , Coronavirus Infections/blood , Coronavirus Infections/epidemiology , Pneumonia, Viral/blood , Pneumonia, Viral/epidemiology , Adult , Age Factors , Antigens, CD/blood , COVID-19 , China , Coronavirus Infections/physiopathology , Female , Humans , Lactate Dehydrogenases/blood , Lymphopenia , Male , Middle Aged , Pandemics , Pneumonia, Viral/physiopathology , SARS-CoV-2 , Singapore , ThrombocytopeniaSubject(s)
Betacoronavirus , Coronavirus Infections , Mycoplasma pneumoniae , Pandemics , Pneumonia, Viral , Adult , Antibodies, Bacterial/blood , COVID-19 , Coinfection , Coronavirus Infections/blood , Coronavirus Infections/complications , Humans , Male , Mycoplasma pneumoniae/immunology , Mycoplasma pneumoniae/isolation & purification , Pneumonia, Mycoplasma/complications , Pneumonia, Viral/blood , Pneumonia, Viral/complications , SARS-CoV-2Subject(s)
Histiocytosis, Langerhans-Cell/diagnosis , Osteolysis/diagnosis , Skull/pathology , Adult , Craniotomy , Diagnosis, Differential , Histiocytosis, Langerhans-Cell/pathology , Histiocytosis, Langerhans-Cell/surgery , Humans , Male , Osteolysis/pathology , Osteolysis/surgery , Predictive Value of Tests , Skull/surgery , Treatment OutcomeABSTRACT
Pityriasis rubra pilaris (PRP) is an idiopathic, papulosquamous inflammatory dermatosis. It is characterized by hyperkeratotic follicular papules coalescing into orange-red scaly plaques, islands of sparing, and palmoplantar keratoderma. PRP can be subdivided into six clinical subtypes according to Griffiths' classification, based on age of onset, disease extent, prognosis, and other associated features. The sixth subtype of PRP occurs in individuals affected by HIV infection, and retroviral screening in all de novo cases of PRP is advised. Other reported associations include various infections, autoimmunity, drugs, and malignancies, although the true significance of these is still unclear. The genetic basis for familial cases, most commonly categorized under the fifth subtype, has been mapped to gain of function mutations in the caspase recruitment domain family, member 14 (CARD14) gene. Treatment of PRP remains a challenge to this day due to a paucity of high-quality evidence. Therapeutic regimens have been guided mostly by case reports and case series, with the mainstay of treatment being oral retinoids. Recently, biologics have emerged as a promising treatment for PRP. We present a review of the clinicopathologic features, pathogenesis, associated disorders, and treatment of PRP, with an emphasis and critical appraisal of the existing literature on the latter.