Management of chronic kidney disease for Maori in Aotearoa New Zealand: a summary of clinical practice guidelines.

AIMS: The kaupapa of the Caring for Australians and New Zealanders with Kidney Impairment (CARI) Clinical practice guidelines for management of chronic kidney disease for Maori in Aotearoa New Zealand is to provide whanau-centred and evidence-based recommendations to healthcare systems, healthcare providers and healthcare workers. The guidelines include screening, identification, management and system-level responses to chronic kidney disease (CKD) to deliver best practice care to Maori affected by CKD across community, primary and secondary services. METHODS: The guidelines are funded by the Ministry of Health - Manatu Hauora and are written by a panel of Maori and non-Maori clinicians and literacy experts across Aotearoa New Zealand from Kaupapa Maori organisations, general practice and nephrology units using standardised methods. The guidelines methodology included consultation with whanau Maori with lived experience of CKD and primary and secondary care practitioners. Additional guideline development would be required to inform management of CKD for non-Maori in Aotearoa New Zealand. RESULTS: The guidelines provide recommendations about equity, governance and accountability, cultural safety, case management, information systems, social determinants of equity and wellbeing and screening. CONCLUSIONS: Recommendations to health services for Maori with CKD are based on giving effect to Te Tiriti o Waitangi and best practice care to prevent CKD, delaying its progression, treating kidney failure through timely transplantation, delivering in community and providing high-quality symptom management.

The loss of OPA1 accelerates intervertebral disc degeneration and osteoarthritis in aged mice.

NP cells of the intervertebral disc and articular chondrocytes reside in avascular and hypoxic tissue niches. As a consequence of these environmental constraints the cells are primarily glycolytic in nature and were long thought to have a minimal reliance on mitochondrial function. Recent studies have challenged this long-held view and highlighted the increasingly important role of mitochondria in the physiology of these tissues. However, the foundational understanding of mechanisms governing mitochondrial dynamics and function in these tissues is lacking. We investigated the role of mitochondrial fusion protein OPA1 in maintaining the spine and knee joint health in mice. OPA1 knockdown in NP cells altered mitochondrial size and cristae shape and increased the oxygen consumption rate without affecting ATP synthesis. OPA1 governed the morphology of multiple organelles, including peroxisomes, early endosomes and cis-Golgi and its loss resulted in the dysregulation of NP cell autophagy. Metabolic profiling and 13C-flux analyses revealed TCA cycle anaplerosis and altered metabolism in OPA1-deficient NP cells. Noteworthy, Opa1AcanCreERT2 mice with Opa1 deletion in disc and cartilage showed age-dependent disc degeneration, osteoarthritis, and vertebral osteopenia. Our findings underscore that OPA1 regulation of mitochondrial dynamics and multi-organelle interactions is critical in preserving metabolic homeostasis of disc and cartilage.

Statewide Initiative to Reduce Patient Radiation Doses During Percutaneous Coronary Intervention.

BACKGROUND: Improved radiation safety practices are needed across hospitals performing percutaneous coronary intervention (PCI). This study was performed to assess the temporal trend in PCI radiation doses concurrent with the conduct of a statewide radiation safety initiative. METHODS: A statewide initiative to reduce PCI radiation doses was conducted in Michigan between 2017 and 2021 and included focused radiation safety education, reporting of institutional radiation doses, and implementation of radiation performance metrics for hospitals. Using data from a large statewide registry, PCI discharges between July 1, 2016, and July 1, 2022, having a procedural air kerma (AK) recorded were analyzed for temporal trends. A multivariable regression analysis was performed to determine whether declines in procedural AK over time were attributable to changes in known predictors of radiation doses. RESULTS: Among 131 619 PCI procedures performed during the study period, a reduction in procedural AK was observed over time, from a median dose of 1.46 (0.86-2.37) Gy in the first year of the study to 0.97 (0.56-1.64) Gy in the last year of the study (P<0.001). The proportion of cases with an AK ≥5 Gy declined from 4.24% to 0.86% over the same time period (P<0.0001). After adjusting for variables known to impact radiation doses, a 1-year increase in the date of PCI was associated with a 7.61% (95% CI, 7.38%-7.84%) reduction in procedural AK (P<0.0001). CONCLUSIONS: Concurrent with the conduct of a statewide initiative to reduce procedural radiation doses, a progressive and significant decline in procedural radiation doses was observed among patients undergoing PCI in the state of Michigan.

A multi-institutional phase I study of acetazolamide with temozolomide in adults with newly diagnosed MGMT-methylated malignant glioma.

Background: A significant unmet need exists for the treatment of glioblastoma, IDH-wildtype (GBM). Preclinical work shows that acetazolamide sensitizes GBM to temozolomide (TMZ) by overcoming TMZ resistance due to BCL-3-dependent upregulation of carbonic anhydrase. Acetazolamide is Food and Drug Administration-approved for the treatment of altitude sickness. Drug repurposing enables the application of drugs to diseases beyond initial indications. This multi-institutional, open-label, phase I trial examined a combination of acetazolamide and TMZ in patients with MGMT promoter-methylated high-grade glioma. Methods: A total of 24 patients (GBM, IDH-wildtype = 22; Grade 4 astrocytoma, IDH-mutant = 1; Grade 3 astrocytoma, IDH-mutant = 1) were accrued over 17 months. All patients received oral acetazolamide (250 mg BID for 7 days increased to 500 mg BID for Days 8-21 of each 28-day cycle) during the adjuvant phase of TMZ for up to 6 cycles. Results: No patient had a dose-limiting toxicity. Adverse events were consistent with known sequelae of acetazolamide and TMZ. In the 23 WHO Grade 4 patients, the median overall survival (OS) was 30.1 months and the median progression-free survival was 16.0 months. The 2-year OS was 60.9%. In total 37% of the study population had high BCL-3 staining and trended toward shorter OS (17.2 months vs N.R., P = .06). Conclusions: The addition of acetazolamide is safe and tolerable in GBM patients receiving standard TMZ. Survival results compare favorably to historical data from randomized trials in patients with MGMT promoter-methylated GBM and support examination of acetazolamide in a randomized trial. BCL-3 expression is a potential biomarker for prognosis in GBM or for patients more likely to benefit from TMZ.

OPA1 protects intervertebral disc and knee joint health in aged mice by maintaining the structure and metabolic functions of mitochondria.

Due to their glycolytic nature and limited vascularity, nucleus pulposus (NP) cells of the intervertebral disc and articular chondrocytes were long thought to have minimal reliance on mitochondrial function. Recent studies have challenged this long-held view and highlighted the increasingly important role of mitochondria in the physiology of these tissues. We investigated the role of mitochondrial fusion protein OPA1 in maintaining the spine and knee joint health in aging mice. OPA1 knockdown in NP cells altered mitochondrial size and cristae shape and increased the oxygen consumption rate without affecting ATP synthesis. OPA1 governed the morphology of multiple organelles, and its loss resulted in the dysregulation of NP cell autophagy. Metabolic profiling and 13 C-flux analyses revealed TCA cycle anaplerosis and altered metabolism in OPA1-deficient NP cells. Noteworthy, Opa1 AcanCreERT2 mice showed age- dependent disc, and cartilage degeneration and vertebral osteopenia. Our findings suggest that OPA1 regulation of mitochondrial dynamics and multi-organelle interactions is critical in preserving metabolic homeostasis of disc and cartilage. Teaser: OPA1 is necessary for the maintenance of intervertebral disc and knee joint health in aging mice.

Postoperative radiotherapy omission in selected patients with early breast cancer following preoperative breast MRI (PROSPECT): primary results of a prospective two-arm study.

BACKGROUND: Adjuvant breast radiotherapy as a standard component of breast-conserving treatment for early cancer can overtreat many women. Breast MRI is the most sensitive modality to assess local tumour burden. The aim of this study was to determine whether a combination of MRI and pathology findings can identify women with truly localised breast cancer who can safely avoid radiotherapy. METHODS: PROSPECT is a prospective, multicentre, two-arm, non-randomised trial of radiotherapy omission in patients selected using preoperative MRI and postoperative tumour pathology. It is being conducted at four academic hospitals in Australia. Women aged 50 years or older with cT1N0 non-triple-negative breast cancer were eligible. Those with apparently unifocal cancer had breast-conserving surgery (BCS) and, if pT1N0 or N1mi, had radiotherapy omitted (group 1). Standard treatment including excision of MRI-detected additional cancers was offered to the others (group 2). All were recommended systemic therapy. The primary outcome was ipsilateral invasive recurrence rate (IIRR) at 5 years in group 1. Primary analysis occurred after the 100th group 1 patient reached 5 years follow-up. Quality-adjusted life-years (QALYs) and cost-effectiveness of the PROSPECT pathway were analysed. This study is registered with the Australian New Zealand Clinical Trials Registry (ACTRN12610000810011). FINDINGS: Between May 17, 2011, and May 6, 2019, 443 patients with breast cancer underwent MRI. Median age was 63·0 years. MRI detected 61 malignant occult lesions separate from the index cancer in 48 patients (11%). Of 201 group 1 patients who had BCS without radiotherapy, the IIRR at 5 years was 1·0% (upper 95% CI 5·4%). In group 1, one local recurrence occurred at 4·5 years and a second at 7·5 years. In group 2, nine patients had mastectomy (2% of total cohort), and the 5-year IIRR was 1·7% (upper 95% CI 6·1%). The only distant metastasis in the entire cohort was genetically distinct from the index cancer. The PROSPECT pathway increased QALYs by 0·019 (95% CI 0·008-0·029) and saved AU$1980 (95% CI 1396-2528) or £953 (672-1216) per patient. INTERPRETATION: PROSPECT suggests that women with unifocal breast cancer on MRI and favourable pathology can safely omit radiotherapy. FUNDING: Breast Cancer Trials, National Breast Cancer Foundation, Cancer Council Victoria, the Royal Melbourne Hospital Foundation, and the Breast Cancer Research Foundation.

The landscape of current research on pediatric diffuse midline glioma: a quantitative analysis of shifts, leaders, and future avenues.

PURPOSE: Diffuse midline glioma (DMG) has seen a surge of research interest in recent years with the growth in knowledge of new avenues for potential treatments. However, no bibliometric review of the field has been conducted to visualize the current state of the field. Here, we use bibliometric mapping to visualize the knowledge structure, collaborations, and trends in the field. METHODS: A total of 1079 original and review articles from 1996 to 2023 on diffuse midline glioma were extracted from the Web of Science Core Collection on June 3, 2023. These files were analyzed with R and VOSviewer to construct bibliometric visualizations. RESULTS: Research interest in DMG has continued to grow, driven by publications of original research. Molecular characterization of DMG has been a key focus of recent literature, and terms relating to novel small molecules, mutations, immunotherapy, the blood-brain barrier, and liquid biopsy may be areas for future growth in the literature. Collaborating nations have generally been the North American and European nations, but other nations have begun to make their mark in the field. Leading and rising institutions and journals are described. CONCLUSION: Research in DMG may continue to focus on molecular characterization and new therapeutics based on this knowledge. Novel collaborations between rising nations and institutions in the field may aid in accelerating this research.

Sirtuin 6 activation rescues the age-related decline in DNA damage repair in primary human chondrocytes.

While advanced age is widely recognized as the greatest risk factor for osteoarthritis (OA), the biological mechanisms behind this connection remain unclear. Previous work has demonstrated that chondrocytes from older cadaveric donors have elevated levels of DNA damage as compared to chondrocytes from younger donors. The purpose of this study was to determine whether a decline in DNA repair efficiency is one explanation for the accumulation of DNA damage with age, and to quantify the improvement in repair with activation of Sirtuin 6 (SIRT6). After acute damage with irradiation, DNA repair was shown to be more efficient in chondrocytes from young (≤45 years old) as compared to middle-aged (50-65 years old) or older (>70 years old) cadaveric donors. Activation of SIRT6 with MDL-800 improved the repair efficiency, while inhibition with EX-527 reduced the rate of repair and increased the percentage of cells that retain high levels of damage. In addition to affecting repair after acute damage, treating chondrocytes from older donors with MDL-800 for 48 hours significantly reduced the amount of baseline DNA damage. Chondrocytes isolated from the knees of mice between 4 months and 22 months of age revealed both an increase in DNA damage with aging, and a decrease in DNA damage following MDL-800 treatment. Lastly, treating murine cartilage explants with MDL-800 lowered the percentage of chondrocytes with high p16 promoter activity, which supports the concept that using SIRT6 activation to maintain low levels of DNA damage may prevent the initiation of senescence.

Redox-active endosomes mediate α5ß1 integrin signaling and promote chondrocyte matrix metalloproteinase production in osteoarthritis.

Mechanical cues sensed by integrins induce cells to produce proteases to remodel the extracellular matrix. Excessive protease production occurs in many degenerative diseases, including osteoarthritis, in which articular cartilage degradation is associated with the genesis of matrix protein fragments that can activate integrins. We investigated the mechanisms by which integrin signals may promote protease production in response to matrix changes in osteoarthritis. Using a fragment of the matrix protein fibronectin (FN) to activate the α5ß1 integrin in primary human chondrocytes, we found that endocytosis of the integrin and FN fragment complex drove the production of the matrix metalloproteinase MMP-13. Activation of α5ß1 by the FN fragment, but not by intact FN, was accompanied by reactive oxygen species (ROS) production initially at the cell surface, then in early endosomes. These ROS-producing endosomes (called redoxosomes) contained the integrin-FN fragment complex, the ROS-producing enzyme NADPH oxidase 2 (NOX2), and SRC, a redox-regulated kinase that promotes MMP-13 production. In contrast, intact FN was endocytosed and trafficked to recycling endosomes without inducing ROS production. Articular cartilage from patients with osteoarthritis showed increased amounts of SRC and the NOX2 complex component p67phox. Furthermore, we observed enhanced localization of SRC and p67phox at early endosomes, suggesting that redoxosomes could transmit and sustain integrin signaling in response to matrix damage. This signaling mechanism not only amplifies the production of matrix-degrading proteases but also establishes a self-perpetuating cycle that contributes to the ongoing degradation of cartilage matrix in osteoarthritis.

Driving Spray Drying towards Better Yield: Tackling a Problem That Sticks Around.

Powder deposition and accumulation on walls of spray drying chamber has been known to impact spray drying processes, resulting in lower yield, frequent shutdowns, and downtimes. Critical factors that impact the extent and rate of wall deposition have been studied extensively in the chemical and food industry. In this paper, we present an atypical process yield issue wherein acceptable yield is obtained during the first batch of spray drying but undergoes significant yield loss in consecutive batches. Through understanding the interplay of the process, material properties, and equipment, we identify key mechanisms that are playing a role in causing the process yield issue. These mechanisms include surface roughness of the inner wall of the spray dryer, variation in gas flow due to the introduction of process analytical technology, start-up and shutdown operating parameters that expose the wall deposited powder from the prior batch to temperatures close to the onset of glass transition temperature and cause depression of its glass transition temperature. These factors result in more wall accumulation and impact the yield in subsequent batches. By correcting for most of these factors, the yield reduction issue was mitigated, and processing efficiency was improved.

Cartilage-specific Sirt6 deficiency represses IGF-1 and enhances osteoarthritis severity in mice.

OBJECTIVES: Prior studies noted that chondrocyte SIRT6 activity is repressed in older chondrocytes rendering cells susceptible to catabolic signalling events implicated in osteoarthritis (OA). This study aimed to define the effect of Sirt6 deficiency on the development of post-traumatic and age-associated OA in mice. METHODS: Male cartilage-specific Sirt6-deficient mice and Sirt6 intact controls underwent destabilisation of the medial meniscus (DMM) or sham surgery at 16 weeks of age and OA severity was analysed at 6 and 10 weeks postsurgery. Age-associated OA was assessed in mice aged 12 and 18 months of age. OA severity was analysed by micro-CT, histomorphometry and scoring of articular cartilage structure, toluidine blue staining and osteophyte formation. SIRT6-regulated pathways were analysed in human chondrocytes by RNA-sequencing, qRT-PCR and immunoblotting. RESULTS: Sirt6-deficient mice displayed enhanced DMM-induced OA severity and accelerated age-associated OA when compared with controls, characterised by increased cartilage damage, osteophyte formation and subchondral bone sclerosis. In chondrocytes, RNA-sequencing revealed that SIRT6 depletion significantly repressed cartilage extracellular matrix (eg, COL2A1) and anabolic growth factor (eg, insulin-like growth factor-1 (IGF-1)) gene expression. Gain-of-function and loss-of-function studies in chondrocytes demonstrated that SIRT6 depletion attenuated, whereas adenoviral overexpression or MDL-800-induced SIRT6 activation promoted IGF-1 signalling by increasing Aktser473 phosphorylation. CONCLUSIONS: SIRT6 deficiency increases post-traumatic and age-associated OA severity in vivo. SIRT6 profoundly regulated the pro-anabolic and pro-survival IGF-1/Akt signalling pathway and suggests that preserving the SIRT6/IGF-1/Akt axis may be necessary to protect cartilage from injury-associated or age-associated OA. Targeted therapies aimed at increasing SIRT6 function could represent a novel strategy to slow or stop OA.

10-Year axillary recurrence in the RACS SNAC1 randomised trial of sentinel lymph node-based management versus routine axillary lymph node dissection.

BACKGROUND: Sentinel node-based management (SNBM) is the international standard of care for early breast cancer that is clinically node-negative based on randomised trials comparing it with axillary lymph node dissection (ALND) and reporting similar rates of axillary recurrence (AR) without distant disease. We report all ARs, overall survival, and breast cancer-specific survival at 10-years in SNAC1. METHODS: 1.088 women with clinically node-negative, unifocal breast cancers 3 cm or less in diameter were randomly assigned to either SNBM with ALND if the sentinel node (SN) was positive, or to SN biopsy followed by ALND regardless of SN involvement. RESULTS: First ARs were more frequent in those assigned SNBM rather than ALND (11 events, cumulative risk at 10-years 1·85%, 95% CI 0·95-3.27% versus 2 events, 0·37%, 95% CI 0·08-1·26%; HR 5·47, 95% CI 1·21-24·63; p = 0·013). Disease-free survival, breast cancer-specific survival, and overall survival were similar in those assigned SNBM versus ALND. Lymphovascular invasion was an independent predictor of AR (HR 6·6, 95% CI 2·25-19·36, p < 0·001). CONCLUSION: First ARs were more frequent with SNBM than ALND in women with small, unifocal breast cancers when all first axillary events were considered. We recommend that studies of axillary treatment should report all ARs to give an accurate indication of treatment effects. The absolute frequency of AR was low in women meeting our eligibility criteria, and SNBM should remain the treatment of choice in this group. However, for those with higher-risk breast cancers, further study is needed because the estimated risk of AR might alter their choice of axillary surgery.

Age and oxidative stress regulate Nrf2 homeostasis in human articular chondrocytes.

OBJECTIVE: The purpose of this study was to investigate the effect of age and oxidative stress on regulation of nuclear factor erythroid-2-related factor 2 (Nrf2) in young, old, and osteoarthritic (OA) human articular chondrocytes. DESIGN: Levels of Nrf2 in primary human chondrocytes isolated from young, old, and OA donors were measured by immunoblotting, qPCR, and immunohistochemistry. Effects on levels of Nrf2, antioxidant proteins regulated by Nrf2, as well as p65, and the anabolic response to insulin-like growth factor-1 (IGF-1) were evaluated after induction of oxidative stress with menadione, Nrf2 knockdown with siRNA, and/or Nrf2 activation with RTA-408. RESULTS: Nrf2 protein levels were significantly lower in older adult chondrocytes (∼0.59 fold; p = 0.034) and OA chondrocytes (∼0.50 fold; p = 0.016) compared to younger cells. Menadione significantly increased Nrf2 protein levels in young chondrocytes by just under four-fold without changes in old chondrocytes. Nrf2 knockdown and activation differentially regulated levels of anti-oxidant proteins including sulfiredoxin and NAD(P)H quinone dehydrogenase 1. Nrf2 activation with RTA-408 also decreased basal p65 phosphorylation, increased aggrecan and type II collagen gene expression, and increased production of proteoglycans in OA chondrocytes treated with IGF-1. CONCLUSIONS: Targeted therapeutic strategies aimed at maintaining Nrf2 activity could be useful in maintaining chondrocyte homeostasis through maintenance of intracellular antioxidant function and redox balance.

Corrigendum: The cGAS-STING pathway affects vertebral bone but does not promote intervertebral disc cell senescence or degeneration.

[This corrects the article DOI: 10.3389/fimmu.2022.882407.].

SIRT6 activation rescues the age-related decline in DNA damage repair in primary human chondrocytes.

While advanced age has long been recognized as the greatest risk factor for osteoarthritis (OA), the biological mechanisms behind this connection remain unclear. Previous work has demonstrated that chondrocytes from older cadaveric donors have elevated levels of DNA damage as compared to chondrocytes from younger donors. The purpose of this study was to determine whether a decline in DNA repair efficiency is one explanation for the accumulation of DNA damage with age, and to quantify the improvement in repair with activation of Sirtuin 6 (SIRT6). Using an acute irradiation model to bring the baseline level of all donors to the same starting point, this study demonstrates a decline in repair efficiency during aging when comparing chondrocytes from young (≤45 years old), middle-aged (50-65 years old), or older (>70 years old) cadaveric donors with no known history of OA or macroscopic cartilage degradation at isolation. Activation of SIRT6 in middle-aged chondrocytes with MDL-800 (20 µM) improved the repair efficiency, while inhibition with EX-527 (10 µM) inhibited the rate of repair and the increased the percentage of cells that retained high levels of damage. Treating chondrocytes from older donors with MDL-800 for 48 hours significantly reduced the amount of DNA damage, despite this damage having accumulated over decades. Lastly, chondrocytes isolated from the proximal femurs of mice between 4 months and 22 months of age revealed both an increase in DNA damage with aging, and a decrease in DNA damage following MDL-800 treatment.

Frailty as a Predictor of Surgical Outcomes Following Femoral Hernia Repair.

BACKGROUND: Femoral hernias are associated with significant morbidity and mortality due to risk of strangulation. Frailty has shown to be strongly associated with adverse outcomes. A modified five-factor frailty index (mFI-5) is a simple validated predictor of postoperative complications and mortality within the ACS-NSQIP® database. This study aims to evaluate the impact of frailty and age on 30-day outcomes after femoral hernia repair. METHODS: Patients who underwent femoral hernia repair were queried using the ACS-NSQIP database (2017) and divided into two groups based on frailty score (FS): Frail (FS = 1-5) and Non-frail (FS = 0). We evaluated the association between postoperative outcomes and frailty, age, sex, presentation, ASA class, timing of surgery, and surgical approaches. Univariate analysis followed by a multivariable logistic regression model was performed to evaluate postoperative morbidity. RESULTS: Of a total of 1,295 patients, 540 (42.7%) were in the Frail group. No differences in sex and race proportions were observed between groups. The Frail group had a higher rate of serious morbidity (4.4% vs 1.9%, P < .001), overall morbidity (7.8% vs 3.4%, P < .010), readmission rate (5.4% vs 2.3%, P = .003), and median (IQR) hospital length of stay (1 [0, 4] vs 0 [0, 1] days, P < .001). In multivariable analysis, male sex, presentation with complication, emergency surgery, and FS were associated with increased odds of overall morbidity. All deaths were in the Frail group. CONCLUSION(S): Frailty, male sex, presentation with obstruction/strangulation, and emergency surgery are independent predictors of increased 30-day morbidity. Thirty-day mortality was noted in the Frail group.

Running footstrike pattern effect on lower extremity work in an individual with transtibial amputation.

Asymmetrical loading favoring the intact limb during running has been associated with increased prevalence of reported knee pain and potential risk factors of knee osteoarthritis in that limb for patients with amputation. Footstrike pattern alterations have been suggested to help alleviate some overloading of the knee, but little is known about how it affects the rest of the limb. The purpose of this case study was to evaluate the effect of footstrike pattern on the distribution of loading throughout the lower extremities during submaximal running of an individual with transtibial amputation (TTA). This study compared loading distribution among the lower extremity joints in a male patient who sustained a TTA and ran using both a rearfoot (RFS) and forefoot strike (FFS) pattern. The results of this case demonstrated that altering footstrike pattern minimally alters the total mechanical work being done by the lower extremities but more so affects the relative amount of work contributed by the individual joints. In the intact limb, the ankle contributes the most to power absorption using a FFS pattern while the knee has a larger role using a RFS pattern. This case suggests that the footstrike pattern affects lower extremity loading distribution at the joint level, and adopting a FFS pattern may alleviate overloading the knee, whereas a RFS pattern may reduce loading at the ankle in individuals with TTA.

Identifying Positive and Negative Factors That Affect the Promotion of Clinical Faculty at the Wayne State University School of Medicine: Does Gender Matter?

INTRODUCTION: Despite well-documented gender disparity in academic medicine, there are many women who achieve success, including successful promotion to associate and full professor status. This study sought to determine whether there was a gender difference in the perception of positive and negative factors affecting the process of promotion to associate or full professor at the Wayne State University School of Medicine (WSUSOM). METHODS: All clinically active associate and full professors who achieved their most recent promotion at the WSUSOM were sent a link to a survey that obtained demographic information as well as the opinions of the respondents regarding what positive and negative factors impacted their most recent promotion. RESULTS: Of the 73 respondents (24%), 58 (19%) were included in our final analysis. Two obstacles ("Lack of interest and encouragement from institutional or departmental leaders" and "Lack of tangible commitment from institutional or departmental leadership [e.g., protected time]") were ranked in the top three ranks by a substantially greater percentage of females than males. Gender-specific networking was seen as significantly more valuable to female faculty members whereas having a stay-at-home partner was seen as significantly more valuable to male faculty members. CONCLUSION: At the WSUSOM, providing more gender-specific networking for women, increasing interest and encouragement from institutional and departmental leaders, and providing a tangible commitment to female faculty from these leaders may help more women to achieve promotion to associate or full professor.