Prolonged treatment of tuberculosis (TB) often leads to poor compliance, default and relapse, converting primary TB patients into category II TB (Cat IITB) cases, many of whom may convert to ...multi-drug resistant TB (MDR-TB). We have evaluated the immunotherapeutic potential of Mycobacterium indicus pranii (MIP) as an adjunct to Anti-Tubercular Treatment (ATT) in Cat II pulmonary TB (PTB) patients in a prospective, randomized, double blind, placebo controlled, multicentric clinical trial. 890 sputum smear positive Cat II PTB patients were randomized to receive either six intra-dermal injections (2 + 4) of heat-killed MIP at a dose of 5 × 10
bacilli or placebo once in 2 weeks for 2 months. Sputum smear and culture examinations were performed at different time points. MIP was safe with no adverse effects. While sputum smear conversion did not show any statistically significant difference, significantly higher number of patients (67.1%) in the MIP group achieved sputum culture conversion at fourth week compared to the placebo (57%) group (p = 0.0002), suggesting a role of MIP in clearance of the bacilli. Since live bacteria are the major contributors for sustained incidence of TB, the potential of MIP in clearance of the bacilli has far reaching implications in controlling the spread of the disease.
Photodynamic therapy (PDT) is a photoactive process that uses the combination of photosensitizers (PSs) and specific wavelengths of light for the treatment of solid tumors and other diseases. PDT ...received increased attention after regulatory approval of several photosensitizing drugs and light applicators worldwide. With the advent of newer PSs, the role of PDT in the treatment of cancer and other diseases has been revolutionized. In addition, various targeting strategies developed for site-specific delivery of PSs will be helpful for avoiding phototoxicity to normal tissues. Receptor-mediated targeted PDT approaches using nanocarriers offer the opportunity of enhancing photodynamic efficiency by directly targeting diseased cells and tissues. At present, clinical application of PDT is well established in medicine and surgery. Successfully used in dermatology, urology, gastroenterology, and neurosurgery, PDT has also seen much progress in basic sciences and clinical photodynamics in recent years. Currently, the use of PDT is just beginning, and more research must be performed to prove its therapeutic efficacy. However, nontoxic compounds involved in PDT provide a certain hope that it will evolve to be an effective mechanism for combating chronic diseases.
Patients with chronic lymphocytic leukemia (CLL) who achieve blood or bone marrow (BM) undetectable minimal residual disease (U-MRD) status after first-line fludarabine, cyclophosphamide, and ...rituximab (FCR) have prolonged progression-free survival (PFS), when assessed by an assay with sensitivity 10−4 (MRD4). Despite reaching U-MRD4, many patients, especially those with unmutated IGHV, subsequently relapse, suggesting residual disease <10−4 threshold and the need for more sensitive MRD evaluation. MRD evaluation by next-generation sequencing (NGS) has a sensitivity of 10−6 (MRD6). To better assess the depth of remission following first-line FCR treatment, we used NGS (Adaptive Biotechnologies Corporation) to assess MRD in 62 patients, all of whom had BM U-MRD by multicolor flow cytometry (sensitivity 10−4) at end-of-FCR treatment. Samples from these patients included 57 BM samples, 29 peripheral blood mononuclear cell (PBMC) samples, and 32 plasma samples. Only 27.4% of the 62 patients had U-MRD by NGS. Rate of U-MRD by NGS was lowest in BM (25%), compared with PBMC (55%) or plasma (75%). No patient with U-MRD by NGS in BM or PBMC was MRD+ in plasma. Patients with mutated IGHV were more likely to have U-MRD by NGS at the end of treatment (EOT; 41% vs 13%, P = .02) than those with unmutated IGHV. Median follow-up was 81.6 months. Patients with U-MRD at EOT had superior PFS vs MRD+ patients, regardless of sample type assessed (BM, P = .02, median not reached NR vs 67 months; PBMC, P = .02, median NR vs 74 months). More sensitive MRD6 testing increases prognostic discrimination over MRD4 testing.
•Most patients with U-MRD by flow cytometry (sensitivity 10−4) after first-line FCR for CLL are MRD+ by NGS (sensitivity 10−6).•Patients with undetectable MRD by NGS have superior PFS.
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Proximal humeral fractures can be treated non-operatively or operatively with open reduction and internal fixation (ORIF) and arthroplasty. Our objective was to assess practice patterns for operative ...and non-operative treatment of proximal humeral fractures. We also report on complications, readmissions, in-hospital mortality, and need for surgery after initial treatment of proximal humeral fractures in California, Florida, and New York.
The State Inpatient Databases and State Emergency Department Databases from the Healthcare Cost and Utilization Project, sponsored by the Agency for Healthcare Research and Quality, were used for the states of California (2005-2011), Florida (2005-2014), and New York (2008-2014). Data on patients with proximal humeral fractures was extracted. Patients underwent non-operative or operative (ORIF or arthroplasty) treatment at baseline and were followed for at least 4 years from the index presentation. If the patient needed subsequent surgery, time to event was calculated in days, and Kaplan-Meier survival curves were plotted.
At the index visit, 90.3% of patients with proximal humeral fractures had non-operative treatment, 6.7% had ORIF, and 3.0% had arthroplasty. 7.6% of patients initially treated non-operatively, 6.6% initially treated with ORIF, and 7.2% initially treated with arthroplasty needed surgery during follow-up. Device complications were the primary reason for readmission in 5.3% of ORIF patients and 6.7% of arthroplasty patients (p < 0.0001). All-cause in-hospital mortality was 9.8% for patients managed non-operatively, 8.8% for ORIF, and 10.0% for arthroplasty (p = 0.003).
A majority of patients with proximal humeral fractures underwent non-operative treatment. There was a relatively high all-cause in-hospital mortality irrespective of treatment. Given the recent debate on operative versus non-operative treatment for proximal humeral fractures, our study provides valuable information on the need for revision surgery after initial treatment. The differences in rates of revision surgery between patients treated non-operatively, with ORIF, and with arthroplasty were small in magnitude. At nine years of follow-up, ORIF had the lowest probability of needing follow-up surgery, and arthroplasty had the highest.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Patients with B-lineage acute lymphoblastic leukemia (ALL) are at high-risk for relapse after allogeneic hematopoietic cell transplantation (HCT). We conducted a single-center phase 2 study ...evaluating the feasibility of 4 cycles of blinatumomab administered every 3 months during the first year after HCT in an effort to mitigate relapse in high-risk ALL patients. Twenty-one of 23 enrolled patients received at least 1 cycle of blinatumomab and were included in the analysis. The median time from HCT to the first cycle of blinatumomab was 78 days (range, 44 to 105). Twelve patients (57%) completed all 4 treatment cycles. Neutropenia was the only grade 4 adverse event (19%). Rates of cytokine release (5% G1) and neurotoxicity (5% G2) were minimal. The cumulative incidence of acute graft-versus-host disease (GVHD) grades 2 to 4 and 3 to 4 were 33% and 5%, respectively; 2 cases of mild (10%) and 1 case of moderate (5%) chronic GVHD were noted. With a median follow-up of 14.3 months, the 1-year overall survival (OS), progression-free survival (PFS), and nonrelapse mortality (NRM) rates were 85%, 71%, and 0%, respectively. In a matched analysis with a contemporary cohort of 57 patients, we found no significant difference between groups regarding blinatumomab's efficacy. Correlative studies of baseline and posttreatment samples identified patients with specific T-cell profiles as “responders” or “nonresponders” to therapy. Responders had higher proportions of effector memory CD8 T-cell subsets. Nonresponders were T-cell deficient and expressed more inhibitory checkpoint molecules, including T-cell immunoglobulin and mucin domain 3 (TIM3). We found that blinatumomab postallogeneic HCT is feasible, and its benefit is dependent on the immune milieu at time of treatment. This paper is posted on ClinicalTrials.gov, study ID: NCT02807883.
•Blinatumomab is safe and feasible for use in B-ALL after allogeneic HCT.•The composition of a patient's T-cell subsets at the time of treatment is indicative of whether they will respond to blinatumomab.
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Physically-demanding occupations may increase rotator cuff disease (RCD) risk and need for surgery. We linked a job-exposure matrix (JEM) to the UK Biobank cohort study to measure physical ...occupational exposures and estimate associations with RCD surgery.
Jobs and UK Standard Occupational Classification (SOC) codes were recorded during the UK Biobank verbal interview. Lifetime job histories were captured through a web-based survey. UK SOC codes were linked to a JEM based on the US O*NET database. O*NET-based scores static strength, dynamic strength, general physical activities, handling/moving objects (range=1-7), time spent using hands, whole body vibration, and cramped/awkward positions (range=1-5) were assigned to jobs. RCD surgeries were identified through linked national hospital inpatient records. Multivariable Cox regression was used to calculate hazard ratios (HR) as estimates of associations with RCD surgery. Among those with lifetime job histories, associations were estimated for duration of time with greatest exposure (top quartile of exposure).
Of 277 808 people reporting jobs, 1997 (0.7%) had an inpatient RCD surgery. After adjusting for age, sex, race, education, area deprivation, and body mass index, all O*NET variables considered were associated with RCD surgery (HR per point increase range=1.10-1.45, all P<0.005). A total of 100 929 people reported lifetime job histories, in which greater exposures were significantly associated with RCD surgery after >10 years of work (eg, HR for 11-20 versus 0 years with static strength score ≥4 = 2.06, 95% confidence interval 1.39-3.04).
Workplace physical demands are an important risk factor for RCD surgery, particularly for workers with more than a decade of exposure.
Mixed phenotype acute leukemia (MPAL) is a rare subtype of acute leukemia characterized by leukemic blasts presenting myeloid and lymphoid markers. Here we report data from integrated genomic ...analysis on 31 MPAL samples and compare molecular profiling with that from acute myeloid leukemia (AML), B cell acute lymphoblastic leukemia (B-ALL), and T cell acute lymphoblastic leukemia (T-ALL). Consistent with the mixed immunophenotype, both AML-type and ALL-type mutations are detected in MPAL. Myeloid-B and myeloid-T MPAL show distinct mutation and methylation signatures that are associated with differences in lineage-commitment gene expressions. Genome-wide methylation comparison among MPAL, AML, B-ALL, and T-ALL sub-classifies MPAL into AML-type and ALL-type MPAL, which is associated with better clinical response when lineage-matched therapy is given. These results elucidate the genetic and epigenetic heterogeneity of MPAL and its genetic distinction from AML, B-ALL, and T-ALL and further provide proof of concept for a molecularly guided precision therapy approach in MPAL.
Rotator cuff myosteatosis following cuff tears is very common and one of the most important prognostic factors in clinical management. Quantitative ultrasound-based imaging techniques (QUBIT) are ...frequently used along with magnetic resonance imaging (MRI) to evaluate rotator cuff fatty degeneration. However, the examination of rotator cuff tissue integrity by QUBIT is lacking a standardized imaging protocol and procedural methodologies. In this scoping review, we synthesized the current state of QUBIT against the reference imaging modalities in patients with rotator cuff tears. The literature search was extracted from 963 studies, with 22 studies included in the final review in accordance with the preferred reporting items for systematic reviews and meta-analyses extensions for scoping reviews. The selected studies included human participants and focused on measuring at least one prognostic or diagnostic factor using ultrasonography-based imaging with reference to MRI. The findings suggest both conventional B-mode ultrasound and shear wave elastography imaging were comparable to MRI-based imaging techniques for the evaluation of fatty infiltration and rotator cuff tear characterization. This review establishes guidelines for reporting shoulder-specific QUBIT aimed at developing a standardized imaging protocol. The objective was to enhance the diagnostic and prognostic capabilities of QUBIT in the clinical setting.
Recommendations for Enhancing Sports Medicine Fellowship Training Jain, Nitin B; Borg-Stein, Joanne; Miranda-Comas, Gerardo ...
American journal of physical medicine & rehabilitation,
2020-April, 2020-04-00, 2020-4-00, 20200401, Letnik:
99, Številka:
4
Journal Article
Recenzirano
Odprti dostop
ABSTRACTPhysical medicine and rehabilitation–trained physicians are increasingly interested in caring for patients with musculoskeletal and sports disorders. Sports medicine fellowships are designed ...to provide competency in sports medicine and musculoskeletal care. The authors, with endorsement from the Association of Academic Physiatrists, provide a framework and tools that Accreditation Council for Graduate Medical Education accredited sports medicine fellowship programs can use to enhance and meet the Accreditation Council for Graduate Medical Education program requirements. Based on the position statement from the American Medical Society for Sports Medicine, we propose recommendations for Accreditation Council for Graduate Medical Education–accredited sports medicine programs to achieve standards of excellence. We also provide recommendations for research requirements during the course of a sports fellowship. With the proposed recommendations, a sports medicine fellowship program can achieve excellence and enhance fellowship training by increasing proficiency in physical medicine and rehabilitation–based skills relevant to sports and musculoskeletal medicine. Given the multidisciplinary nature of musculoskeletal and sports medicine, it is also key that fellowship programs (regardless of the department that they are accredited through) have faculty members that represents these disciplines and accept applicants with residency training in physical medicine and rehabilitation, internal medicine, family medicine, pediatrics, and emergency medicine.
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