Recent developments in fetal therapy
Hung N. Winn, Frank A. Chervenak, Roberto Romero in Clinical Maternal-Fetal Medicine Online, 2021
Although the overall benefit of bladder shunting seems to translate into increased survival (OR 2.5; 95% CI, 1.0–5.9; p < 0.03) especially in the most severe cases (OR 8; 95% CI, 1.2–52.9; p < 0.03) (41), this hardly translates into improved renal function. Several potential explanations have recently been identified: Shunting is performed under local anesthesia to the mother as well as fetal analgesia and curarization. Shunts most commonly used are 2.5mm in diameter and placed through a 3.5mm trocar introduced percutaneously into the uterus and into the fetal bladder. It is not an easy procedure to perform and one-fourth to one-third of shunts get displaced.Shunting should optimally be performed when renal function is still normal. The best single parameter seems to be beta-2-microglobulin in fetal blood since fetal urine analysis and ultrasound assessment of the kidneys have a poor predictive value.The diagnosis of PUV is the only one amenable to significant improvement in survival and renal function. However, the diagnosis is rightly made in only around 60% of the cases in experienced hands.Overall, it is likely that shunting is too often being placed to late in the course of the natural history of the disease.
Test Paper 1
Teck Yew Chin, Susan Cheng Shelmerdine, Akash Ganguly, Chinedum Anosike in Get Through, 2017
Amyloid arthropathy most typically affects the shoulders, carpal bones and hips in a bilateral fashion. It is typically associated with long-term renal dialysis, which results in deposition of the beta-2 microglobulin. Affected joints demonstrate subchondral cystic lesions with juxta-articular swelling. The presence of low-to-intermediate signal soft tissue within and around the joint clinches the diagnosis, as this represents the signal characteristics of the deposited proteins (cf. other inflammatory/infectious arthropathies, which tend to produce higher water content thansoft-tissue changes in the joint). Joint space is also typically preserved until the late stages of disease, similar to gout.
The Non-Hodgkin’s Lymphomas and Plasma Cell Dyscrasias
Harold R. Schumacher, William A. Rock, Sanford A. Stass in Handbook of Hematologic Pathology, 2019
Plasma cell myeloma is a progressive disease with a poor prognosis. The median survival with conventional therapy is approximately 3 years. The length of survival is closely related to the stage of the disease at diagnosis. Patients are monitored with periodic determinations of serum and urine M-protein levels, and serum beta-2 microglobulin levels. Elevated levels of serum beta-2 microglobulin are associated with progressive disease and a worse prognosis. Complete remissions are unusual, and patients die of the disease. Infection is the most common cause of death. Renal failure is a contributing factor in many cases.
Effect of clinical factors on trajectory of functional performance in patients undergoing hemodialysis
Published in Renal Failure, 2021
Jin-Bor Chen, Lung-Chih Li, Wen-Chin Lee, Sin- Hua Moi, Cheng-Hong Yang
We attempted to determine the association between uremic toxins and trajectory of functional performance in patients undergoing HD. We analyzed this association with the indicators of small uremic solutes and middle molecules in circulation. Our result did not exhibit a positive association between uremic toxins and trajectory of KPS scales in patients undergoing HD, except with BUN and beta-2-microglobulin. In our previous study, we found that BUN was one of the major determinants of functional performance in patients undergoing HD by the classification and regression tree approach [8]. It is well known that HD patients have high beta-2-microglobulin levels [22]. The deposit of beta-2-microglobulin is mainly in musculoskeletal system. The preferential deposition in tendons and bones can result in physical functional impairment [22–24]. Our findings elicit a hypothesized strategy to utilize large-pore hemodialyzers to remove large-size uremic toxins. The effects of improving physical functional impairment by these hemodialyzers in HD patients warrant to be investigated in the future. Our study also implied that holistic evaluation should be taken into account in making decisions for the management of impaired functional performance in patients undergoing HD. It is concerned with not only dialysis adequacy but also other potential contributors in clinical scenario.
Cumulative experience and long term follow-up of pentostatin-based chemoimmunotherapy trials for patients with chronic lymphocytic leukemia
Published in Expert Review of Hematology, 2018
Neil E. Kay, Betsy R. LaPlant, Adam M. Pettinger, Timothy G. Call, Jose F. Leis, Wei Ding, Sameer A. Parikh, Michael J. Conte, Deborah A. Bowen, Tait D. Shanafelt
Table 1 summarizes the major features of the patient cohorts receiving the 7 pentostatin-based CIT regimens. There were 288 evaluable patients treated on these trials with a median age of 65 overall but ages varied from 38 to 83 years of age. Males were entered on the trials at a 3:1 ratio compared to females. IGVH mutation status was approximately equal with 52.4% having unmutated IGVH versus 42.4% with mutated IGVH status (5.2% missing IGVH status). FISH status according to the Dohner Hierarchy [16] at entry to the trials included the following: del17p (4.5%), del11q (14.9%), trisomy 12 (20.8%), del13q (34.0%), normal (20.5%) and other (4.9%). The median serum beta 2 microglobulin was 3.8 mg/mL (range 0.3–14.7). Other novel prognostic factors in this cohort included significant numbers of patients who were ZAP 70+ (45.1%), CD38 + (37.8%) and CD49d + (39.9%). Using the CLL International Prognostic Index (CLL-IPI), 18 (6.3%) of patients could not be classified, 11 patients were categorized as having very high risk (3.8%), 131 patients having high risk (45.5%), 95 as having intermediate risk (33.0%), and 33 having low risk (11.5%). In total, the trial cohorts were viewed as predominantly adverse patients based on their IGVH and FISH status, as well as the flow-based prognostic markers and CLL IPI risk groups.
Avapritinib for Systemic Mastocytosis
Published in Expert Review of Hematology, 2021
Prithviraj Bose, Srdan Verstovsek
A key concept is that the KIT D816V mutation is not restricted to the neoplastic mast cells, but is also found in other cell types in the bone marrow, e.g. eosinophils, monocytes, thus making it a better indicator of overall disease burden in patients with SM-AHN than traditional measures of mast cell burden, such as serum tryptase levels and the percentage of mast cells in the bone marrow [20–22]. Conversely, several other mutations commonly encountered in myeloid malignancies have been demonstrated in both mast cells and other cell types involved in the AHN in the bone marrow of SM patients [23,24]. Some of these have been found to be prognostically adverse, viz., SRSF2, ASXL1, RUNX1 (the so-called ‘S/A/R’ mutations) [25], EZH2 [26], NRAS [27] and DNMT3A [28]. A number of prognostic models for AdvSM, incorporating just clinical [16] or a combination of clinical and genomic variables [27,29], have recently been published. A recent study by the European Competence Network on Mastocytosis (ECNM) found only age ≥60 years and serum alkaline phosphatase ≥100 U/L to be prognostic for overall survival (OS) in non-advanced SM [16]. Serum beta-2-microglobulin levels have been shown to powerfully predict progression in non-advanced SM [28].
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