Sex and gender differences in lower limb chronic exertional compartment syndrome: a systematic review.

OBJECTIVES: Chronic exertional compartment syndrome (CECS) is a cause of exertional leg pain and has been reported in varying frequencies in males and females. Currently, it is unclear whether there are significant sex and gender differences in lower-limb CECS. Delineating sex and gender differences is vital in determining the causes of CECS and best treatments. This systematic review aimed to determine the sex/gender distribution of CECS and to assess for sex and gender differences in CECS diagnosis and outcomes. METHODS: PubMed (Medline), Cochrane Library, and EMBASE databases were searched for studies that were published from January 2000-March 2022 and reported lower-limb CECS data in males and/or females. Data on CECS diagnosis (intracompartmental pressures) and outcomes (e.g. post-surgical return-to-sport, need for re-operation) with sex/gender breakdowns were extracted. The sex/gender distribution of CECS and prevalence of CECS by sex/gender were calculated. RESULTS: Forty-one studies were included in the systematic review; there were 27 retrospective reviews, 8 prospective studies, and 6 retrospective studies with prospective follow-ups. Thirty studies involved surgical populations. Sex/gender distribution of CECS was calculated using data from 24 studies; 51% were female. Prevalence of CECS was available in five studies and ranged widely for males (54%-73%) and females (43%-65%). Intracompartmental pressure data varied by sex/gender. Male athletes were more likely than female athletes to return to sport following surgery for CECS, but variations in all other post-surgical outcomes were observed between sexes and genders in the general population. CONCLUSION: Females represented 51% of the patients who were diagnosed with CECS among studies. Most CECS diagnosis and outcomes data varied by sex/gender, except for post-surgical outcomes data in athletes, which demonstrated that males had higher rates of return to sport than females. Future studies are needed to examine factors contributing to sex and gender differences in CECS diagnosis and outcomes.

Variability in Patient-Incurred Costs and Protocols of Regenerative Medicine Procedures for Musculoskeletal Conditions in the United States.

Background: The use of regenerative medicine as an "off label" treatment for musculoskeletal conditions has increased in recent years. However, the literature is sparse regarding the costs of these treatments to patients. Purposes: We sought to determine the patient-incurred costs for regenerative medicine treatments performed by physicians for musculoskeletal conditions in the United States, according to primary specialty, geographic region, practice setting, and years in practice. We also sought to characterize pre- and posttreatment protocols and image guidance use. Methods: We performed a cross-sectional study with data collection occurring between April 2020 and April 2021. It began with the distribution of an online survey through an email campaign by the American College of Sports Medicine to its members. Approximately 90 emails were sent by our research team as well. Throughout the year, various participant recruitment methods were used (through Twitter, for example). Survey data included physician demographics, practice/training information, types/costs of regenerative medicine treatments performed, and pre-/postprocedure protocols. Results: One hundred physicians who self-reported performing standalone regenerative medicine procedures participated in this online survey. According to the responses, the most common treatments performed were platelet-rich plasma (PRP; 100%), bone marrow concentrate (BMC; 41%), microfragmented adipose grafting (36%), prolotherapy (33%), and bone marrow aspirate (BMA; 21%) administered to the peripheral joints, tendons/muscles, ligaments, and/or spine. Overall, the respondents reported large variations in treatment costs to patients; BMA and BMC were the most expensive and had the largest ranges in costs for all anatomical locations. Costs for PRP were lower than those for BMA and BMC, with less variation. Physicians in private practice reported higher PRP, BMC, and BMA costs in the peripheral joints than those in academic settings. Most physicians recommended avoiding non-steroidal anti-inflammatory drugs pre- and postprocedure, and 74% recommended physical therapy postprocedure. Conclusions: Findings from a survey of physicians who provide regenerative medicine procedures as off-label treatment for musculoskeletal conditions suggest that there is variation in related patient-incurred costs. Future studies should explore associations between treatment costs and outcomes.

Clinical outcomes following intradiscal injections of higher-concentration platelet-rich plasma in patients with chronic lumbar discogenic pain.

PURPOSE: This study aimed to assess clinical outcomes following intradiscal injections of higher-concentration (> 10 ×) platelet-rich plasma (PRP) in patients with chronic lumbar discogenic pain and to compare outcomes with a historical cohort. METHODS: This retrospective study included 37 patients who received intradiscal injections of higher-concentration (> 10 ×) PRP and had post-procedure outcomes data (visual numerical scale pain score, Functional Rating Index [FRI], and NASS Patient Satisfaction Index). Outcomes were compared to a historical cohort of 29 patients who received intradiscal injections of < 5X PRP. RESULTS: Pain and FRI scores significantly improved by 3.4 ± 2.5 and 46.4 ± 27.6, respectively, at 18.3 ± 13.3 months following intradiscal injections of > 10 × PRP (p < 0.001). These improvements were greater than those reported by the historical cohort (1.7 ± 1.6 and 33.7 ± 12.3; p = 0.004 and 0.016, respectively). Additionally, the satisfaction rate was higher in patients receiving > 10 × PRP compared to those receiving < 5 × PRP (81% vs. 55%; p = 0.032). CONCLUSIONS: Findings from this study suggest that clinical outcomes can be optimized by using PRP preparations that contain a higher concentration of platelets. Further research is needed to continue to optimize the composition of PRP used to treat patients with lumbar disc disease.

Loss of heterochromatin and retrotransposon silencing as determinants in oocyte aging.

Mammalian oocyte quality reduces with age. We show that prior to the occurrence of significant aneuploidy (9M in mouse), heterochromatin histone marks are lost, and oocyte maturation is impaired. This loss occurs in both constitutive and facultative heterochromatin marks but not in euchromatic active marks. We show that heterochromatin loss with age also occurs in human prophase I-arrested oocytes. Moreover, heterochromatin loss is accompanied in mouse oocytes by an increase in RNA processing and associated with an elevation in L1 and IAP retrotransposon expression and in DNA damage and DNA repair proteins nuclear localization. Artificial inhibition of the heterochromatin machinery in young oocytes causes an elevation in retrotransposon expression and oocyte maturation defects. Inhibiting retrotransposon reverse-transcriptase through azidothymidine (AZT) treatment in older oocytes partially rescues their maturation defects and activity of the DNA repair machinery. Moreover, activating the heterochromatin machinery via treatment with the SIRT1 activating molecule SRT-1720, or overexpression of Sirt1 or Ezh2 via plasmid electroporation into older oocytes causes an upregulation in constitutive heterochromatin, downregulation of retrotransposon expression, and elevated maturation rates. Collectively, our work demonstrates a significant process in oocyte aging, characterized by the loss of heterochromatin-associated chromatin marks and activation of specific retrotransposons, which cause DNA damage and impair oocyte maturation.

Race- and Gender-Based Differences in Descriptions of Applicants in the Letters of Recommendation for Orthopaedic Surgery Residency.

BACKGROUND: Letters of recommendation (LOR) are an important component of trainee advancement and assessment. Examination of word use in LOR has demonstrated significant differences in how letter writers describe female and male applicants. Given the emphasis on increasing both gender and racial diversity among orthopaedic surgeons, we aimed to study gender and racial differences in LOR for applicants to orthopaedic surgery residencies. METHODS: All applications submitted to a single, academic orthopaedic residency program in 2018 were included. Self-identified gender and race were recorded. The LOR were analyzed via a text analysis software program using previously described categories of communal, agentic, grindstone, ability, and standout words. We examined the relative frequency of word use in letters for (1) male and female applicants and (2) white and underrepresented in orthopaedics (UiO) applicants, with the subgroup analysis based on whether standardized (using the American Orthopaedic Association template) or traditional (narrative) LOR were used. RESULTS: Two thousand six hundred twenty-five LOR were submitted for 730 applicants (79% men). Fifty-nine percent of applicants were self-identified as white, and 34% were self-identified as UiO. In traditional LOR, standout words (odds ratio [OR] 1.07; p = 0.01) were more likely to be used in letters for women compared with men, with no difference in any other word-use category. In standardized LOR, there were no gender-based differences in any word category. In traditional LOR, grindstone words (OR = 0.96; p = 0.02) were more likely to be used in letters for UiO than white applicants, whereas standout words (OR = 1.05; p = 0.04) were more likely to be used in letters for white candidates. In standardized LOR, there were no race-based differences in any word category use. CONCLUSIONS: Small differences were found in the categories of words used to describe male and female candidates and white and UiO candidates. These differences were not present in the standardized LOR compared with traditional LOR. It is possible that the use of standardized LOR may reduce gender- and race-based bias in the narrative assessment of applicants.

Predictive value of TP53 fluorescence in situ hybridization in cytogenetic subgroups of acute myeloid leukemia.

Acute myeloid leukemia (AML) with a complex karyotype (CK) has frequent alterations in TP53 and a very poor prognosis. We examined whether a prompt and simple fluorescence in situ hybridization (FISH) analysis for 17p13 deletion at diagnosis has a predictive value for response to therapy and overall survival in subgroups of AML. In 15 patients with a normal karyotype the TP53 FISH analysis was normal, whereas in 16 patients with CK 75% had only one copy of the TP53 allele. The deletion was also detected in 33% of six patients with monosomy or partial monosomy of chromosome 5, 7, 9, or 12. This loss of TP53 correlated significantly with a poor response to chemotherapy, and the median survival time of these patients was shorter. TP53 FISH analysis carried out at diagnosis has a predictive value with respect to chemotherapy response and can therefore facilitate a rapid decision on treatment strategies.

Co-existence of multiple subclones in TEL-AML1 at diagnosis of acute lymphoblastic leukaemia in association with submicroscopic deletion of AML1.

The TEL/AML1 (ETV6/RUNX1) fusion gene is the most common genetic rearrangement in paediatric acute lymphoblastic leukaemia (ALL). Although considered to be a low-risk leukaemia, it is associated with a relapse rate of 10-20%. The coexistence of different subclones at diagnosis, based on polymerase chain reaction (PCR) studies of IG/TCR gene rearrangement, with differential response to chemotherapy, was recently reported in this subtype of ALL. We wished to demonstrate such subclones at diagnosis by a recently developed technique of quantitative multiparametric fluorescence in situ hybridization (FISH). Bone marrow cells from 80 paediatric patients with ALL at diagnosis were analysed for the presence of the TEL/AML1 fusion gene by interphase FISH. Fourteen patients were positive for the translocation. Four of them had several subclones associated with various combinations of additional chromosomal abnormalities. The most striking was an atypical and unexpected hybridization pattern consistent with a submicroscopic deletion of the 5' region of the AML1 breakpoint. Other abnormalities included TEL deletion, trisomy and tetrasomy 21 as well as double TEL-AML1 fusion. The presence of numerous subclones in about 25% of patients with TEL/AML1+ ALL suggests extensive clonal evolution by the time of diagnosis.

Determination of chromosome 13 status in bone marrow cells of patients with multiple myeloma using combined morphologic and fluorescence in situ hybridization analysis.

Deletion of chromosome 13q is believed to be an adverse prognostic marker in patients with multiple myeloma (MM). Interphase fluorescence in situ hybridization (I-FISH) is the method of choice for detection of chromosome 13q deletion (del13q). However, I-FISH has high false-positive rates attributed to a low percentage of plasma cells (PC), which are responsible for MM, in bone marrow (BM) samples from MM patients. In an attempt to overcome this problem, combined morphologic and I-FISH analyses were performed by a unique system that allows rapid automatic scanning of a large number of cells with simultaneous determination of the lineage of specific cells carrying del13q. The percentage of PC with del13q in BM samples from 40 MM patients was calculated. In addition, we established a useful prognostic ratio defined as the number of PC with del13q divided by the number of non-PC with del13q (PDP/PDNP), which may help to precisely define the putative role of del13q in prediction response of MM patients to new therapeutic compounds. We suggest this technique as a novel sensitive and specific method for detection of del13q in a minor PC population of MM patients.