Proximal hamstring avulsion repair resulted in superior outcomes as compared with nonoperative treatment, although the complication rate was 23.17%. The nonoperative group was quite small, making a true comparison difficult. Acute repairs have better outcomes than do chronic repairs. Complete avulsion repairs had higher patient satisfaction, less pain, and a higher complication rate than partial avulsion repairs, although partial avulsion repairs had better hamstring strength and endurance. Studies of high methodological quality are lacking in terms of investigating the outcomes of proximal hamstring avulsion repairs.
Immune checkpoint inhibitors (ICIs) have recently revolutionized cancer treatment, providing unprecedented clinical benefits. However, primary or acquired therapy resistance can affect up to two-thirds of patients receiving ICIs, underscoring the urgency to elucidate the mechanisms of treatment resistance and to design more effective therapeutic strategies. Conventional cancer treatments, including cytotoxic chemotherapy, radiation therapy, and targeted therapy, have immunomodulatory effects in addition to direct cancer cell-killing activities. Their clinical utilities in combination with ICIs have been explored, aiming to achieve synergetic effects with improved and durable clinical response. Here, we will review the immunomodulatory effects of chemotherapy, targeted therapy, and radiation therapy, in the setting of ICI, and their clinical implications in reshaping modern cancer immunotherapy.
Premature graying of hair (PGH) is defined as graying of hair before the age of 20 years in Caucasians and before 30 years in African American population. It can severely affect the self-esteem of an individual. The exact etiopathogenesis remains unknown, although it has been associated with premature aging disorders, atopy, and autoimmune diseases. Patients, who present with PGH, should be assessed for syndromes and metabolism diseases. Hair dyes remain the main modality of the treatment for cosmetic concerns after nutritional supplementation.
Trichotillomania (hair pulling disorder) is a fairly common but underreported disorder characterized by recurrent episodes of pulling hair from different parts of the body. Currently classified in Diagnostic and Statistical Manual of Psychiatric Disorders (DSM-5) under the heading of the "Obsessive-compulsive spectrum and related disorders." The estimated prevalence data suggest that 0.5-2% of the general population suffers from this disorder. Stress and anxiety are directly correlated to the production of trichotillomania symptoms. The psychosocial aspects of trichotillomania are greatly underestimated, but recent literature suggests an increased interest in this neglected area. Although no FDA approved medications are available for the treatment of trichotillomania, a variety of medications including N-acetylcysteine have shown benefit in case reports. Combined liaison clinics, with an interdisciplinary approach, are highly advisable in the treatment of these cases.
Botulinum toxin, also called the "miracle toxin," is a neurotoxin produced by the bacteria Clostridium botulinum. It is known to block nerve signals that contract muscles resulting in a temporary paralysis of the muscles. Toxins type A and B have been extensively studied and utilized in the realm of beauty and cosmetology. Initially, the toxin gained popularity as a disease-causing "poison". It was only later that it found its way to becoming a must have in modern aesthetic practice. Today, this wonder toxin has proven to be an apt and convenient option in the field of anti-aging medicine.
Most bladder cancers are early-stage tumors known as papillary non-muscle-invasive bladder cancer (NMIBC). After resection, up to 70% of NMIBCs recur locally, and up to 20% of these recurrences progress to muscle invasion. There is an unmet need for additional biomarkers for stratifying tumors based on their risk of recurrence and progression. We previously identified as among the most commonly mutated genes in NMIBC and provided initial evidence in a pilot cohort that-mutant tumors recurred less frequently than wild-type tumors. Here, we report a STAG2 biomarker validation study using two independent cohorts of clinically annotated papillary NMIBC tumors from the United States and Europe. The value of STAG2 immunostaining for prediction of recurrence was initially evaluated in a cohort of 82 patients with papillary NMIBC ("Georgetown cohort"). Next, the value of STAG2 immunostaining for prediction of progression to muscle invasion was evaluated in a progressor-enriched cohort of 253 patients with papillary NMIBC ("Aarhus cohort"). In the Georgetown cohort, 52% of NMIBC tumors with intact STAG2 expression recurred, whereas 25% of STAG2-deficient tumors recurred ( = 0.02). Multivariable analysis identified intact expression as an independent predictor of recurrence (HR = 2.4; = 0.05). In the progressor-enriched Aarhus cohort, 38% of tumors with intact STAG2 expression progressed within 5 years, versus 16% of STAG2-deficient tumors ( < 0.01). Multivariable analysis identified intact STAG2 expression as an independent predictor of progression (HR = 1.86; = 0.05). STAG2 IHC is a simple, binary, new assay for risk stratification in papillary NMIBC. .
Background: Few studies support treating morphea (localized scleroderma) with hydroxychloroquine. Objective: To assess the efficacy of hydroxychloroquine treatment of morphea. Methods: We conducted a retrospective study of 84 patients who had morphea and were treated with hydroxychloroquine monotherapy for at least 6 months at our institution from 1996 through 2013. The median times to initial and maximal responses were assessed. Results: Of 84 patients (median age at diagnosis, 29.5 years), 65 (77.4%) were female; 36 (42.9%) had a complete response to hydroxychloroquine; 32 (38.1%) had a partial response greater than 50%; 10 (11.9%) had a partial response less than or equal to 50%; and 6 (7.1%) had no response. The median time to initial response was 4 months; the median time to maximal response was 12 months. Ten patients (11.9%) experienced adverse effects from hydroxychloroquine; the most common was nausea (6 patients). Limitations: Retrospective study. Conclusions: Hydroxychloroquine is a valuable treatment for morphea because of its high response rate and low rate of adverse effects; however, prospective studies are needed to determine its true efficacy.
Management of PD-1 blockade resistance in metastatic melanoma (MM) remains challenging. Immunotherapy or chemotherapy alone provides limited benefit in this setting. Chemo-immunotherapy (CIT) has demonstrated favorable efficacy and safety profiles in lung cancer. Our pre-clinical study showed that in MM patients who have failed PD-1 blockade, the addition of chemotherapy increases CX3CR1+ therapy-responsive CD8+ T-cells with enhanced anti-tumor activity, resulting in improved clinical response. Here, we examined the clinical outcomes of CIT in MM patients after PD-1 blockade failure and the treatment-related changes in CX3CR1+ therapy-responsive CD8+ T-cells. We reviewed MM patients seen between January 2012 and June 2018 who failed anti-PD-1-based therapy and received subsequent CIT, immune checkpoint inhibitors (ICI) or chemotherapy alone. Overall survival (OS), objective response rate (ORR), event-free survival (EFS), and toxicities were assessed. Among 60 patients, 33 received CIT upon disease progression on PD-1 blockade. At a median follow-up of 3.9 years, the CIT group had a median OS of 3.5 years [95% confidence interval (CI) 1.7–NR] vs. 1.8 years (95% CI 0.9–2; P = 0.002) for those who received subsequent ICI (n = 9) or chemotherapy alone (n = 18), with ORR of 59% vs. 15% (P = 0.0003), respectively. The median EFS was 7.6 months (95% CI 6–10) following CIT vs. 3.4 months (95% CI 2.8–4.1; P = 0.0005) following ICI or chemotherapy alone. Therapy-responsive CX3CR1+CD8+ T-cells showed dynamic increase with successful CIT. CIT showed favorable clinical outcomes and acceptable safety profile in PD-1 blockade-resistant patients. CX3CR1+CD8+ therapy-responsive T-cells can be potentially used for monitoring disease response to CIT.
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