Physician Health Series, Part 3: Physician Mental Health.

This article is the third of 3 articles in a series about managing the care of physicians as patients. In part 1, the authors reviewed unique characteristics of physicians as patients with some general guidance for how to approach their care. Part 2 highlighted role clarity for the treating physician with discussion of the physical and cognitive issues that commonly arise when treating physician-patients along with licensure issues and reporting requirements. This final installment will focus on physician mental health and work-related stress.

Part Two: Managing Physicians as Patients and Their Safe Return to Work.

This second installment in a 3-part series about physicians as patients explores challenges in communication and role definition while managing their care and safe return to work. In the first article of the series, authors reviewed unique characteristics that make physicians different as patients, with some general guidance about how to approach their care. Although most treating physicians receive little occupational training, health issues commonly have an impact on work with imperative to address work issues promptly for best outcome. This paper demystifies the challenge of managing work status and discusses navigating common physical and cognitive issues while maintaining role clarity. The treating clinician reading this paper will learn to avoid common pitfalls and be better equipped to provide initial assessments and interventions to keep physicians working safely, keeping in mind licensure issues and reporting requirements. Part Three of the series will focus on the most common mental health issues seen in physicians.

Novel high molecular weight polymerized hemoglobin in a non-obese model of cardiovascular and metabolic dysfunction.

The widespread adoption of high-calorie, high-fat, high-sucrose diets (HFHSD) has become a global health concern, particularly due to their association with cardiovascular diseases and metabolic disorders. These comorbidities increase susceptibility to severe outcomes from viral infections and trauma, with trauma-related incidents significantly contributing to global mortality rates. This context underscores the critical need for a reliable blood supply. Recent research has focused on high molecular weight (MW) polymerized human hemoglobin (PolyhHb) as a promising alternative to red blood cells (RBCs), showing encouraging outcomes in previous studies. Given the overlap of metabolic disorders and trauma-related health issues, it is crucial to assess the potential toxicity of PolyhHb transfusions, particularly in models that represent these vulnerable populations. This study evaluated the effects of PolyhHb exchange transfusion in guinea pigs that had developed metabolic disorders due to a 12-week HFHSD regimen. The guinea pigs, underwent a 20 % blood volume exchange transfusion with either PolyhHb or the lower molecular weight polymerized bovine hemoglobin, Oxyglobin. Results revealed that both PolyhHb and Oxyglobin transfusions led to liver damage, with a more pronounced effect observed in HFHSD-fed animals. Additionally, markers of cardiac dysfunction indicated signs of cardiac injury in both the HFHSD and normal diet groups following the Oxyglobin transfusion. This study highlights how pre-existing metabolic disorders can exacerbate the potential side effects of hemoglobin-based oxygen carriers (HBOCs). Importantly, the newer generation of high MW PolyhHb showed lower cardiac toxicity compared to the earlier generation low MW PolyhHb, known as Oxyglobin, even in models with pre-existing endothelial and metabolic challenges.

Physician Health Series Part One: Characteristics of Physicians as Patients.

This is the first article of a 3-part series about physician health. In this installment, we outline the unique characteristics of physicians as patients, challenges and opportunities presented by physician-patients, and recommendations for treating physicians. Future articles will delve into role clarity, occupational considerations, mental health, and interactions with third parties such as the physician's employer or licensing board. Ultimately, this series will help treating clinicians provide the best care to their physician-patients and successfully navigate the unique challenges that may arise, especially when the diagnosis may have an impact on their ability to practice medicine.

Colon Cancer Survival Among South Asian Americans: A Cross-Sectional Analysis of a National Dataset.

INTRODUCTION: Colon cancer (CC) is one of the most common cancers among South Asian Americans (SAAs). The objective of this study was to measure differences in risk-adjusted survival among SAAs with CC compared to non-Hispanic Whites (NHWs) using a representative national dataset from the United States. METHODS: A retrospective analysis of patients with CC in the National Cancer Database (2004-2020) was performed. Differences in presentation, management, median overall survival (OS), three-year survival, and five-year survival between SAAs and NHWs were compared. Kaplan-Meier analysis and multivariable Cox regression were used to assess differences in survival outcomes, adjusting for demographics, presentation, and treatments received. RESULTS: Data from 2873 SAA and 639,488 NHW patients with CC were analyzed. SAAs were younger at diagnosis (62.2 versus 69.5 y, P < 0.001), higher stage (stage III [29.0% versus 26.2%, P = 0.001] or Stage IV [21.4% versus 20.0%, P = 0.001]), and experienced delays to first treatment (SAA 5.9% versus 4.9%, P = 0.003). SAAs with CC had higher OS (median not achieved versus 68.1 mo for NHWs), three-year survival (76.3% versus 63.4%), and five-year survival (69.1% versus 52.9%). On multivariable Cox regression, SAAs with CC had a lower risk of death across all stages (hazard ratio: 0.64, P < 0.001). CONCLUSIONS: In this national study, SAA patients with CC presented earlier in life with more advanced disease, and a higher proportion experienced treatment delay compared to NHW patients. Despite these differences, SAAs had better adjusted OS than NHW, warranting further exploration of tumor biology and socioeconomic determinants of cancer outcomes in SAAs.

Effectiveness of population-based recovery actions for threatened southern mountain caribou.

Habitat loss is affecting many species, including the southern mountain caribou (Rangifer tarandus caribou) population in western North America. Over the last half century, this threatened caribou population's range and abundance have dramatically contracted. An integrated population model was used to analyze 51 years (1973-2023) of demographic data from 40 southern mountain caribou subpopulations to assess the effectiveness of population-based recovery actions at increasing population growth. Reducing potential limiting factors on threatened caribou populations offered a rare opportunity to identify the causes of decline and assess methods of recovery. Southern mountain caribou abundance declined by 51% between 1991 and 2023, and 37% of subpopulations were functionally extirpated. Wolf reduction was the only recovery action that consistently increased population growth when applied in isolation, and combinations of wolf reductions with maternal penning or supplemental feeding provided rapid growth but were applied to only four subpopulations. As of 2023, recovery actions have increased the abundance of southern mountain caribou by 52%, compared to a simulation with no interventions. When predation pressure was reduced, rapid population growth was observed, even under contemporary climate change and high levels of habitat loss. Unless predation is reduced, caribou subpopulations will continue to be extirpated well before habitat conservation and restoration can become effective.

Treatment of Oligometastatic GI Cancers.

Oligometastatic state is believed to potentially represent a transitional stage between early, locoregional state disease and widely metastatic disease. Historically, locoregional approaches, particularly in advanced colorectal cancers, have demonstrated efficacy in select patients with limited burden of metastatic disease. Recent strides in systemic therapies, including biomarker-based treatments and immunotherapy, alongside innovations in surgical techniques and novel locoregional approaches such as stereotactic radiotherapy and ablation, have ushered in a new era of therapeutic possibilities across all oligometastatic GI cancers. Despite these advancements, there remains a significant gap in high-quality prospective evidence guiding patient selection and treatment decisions across various disease types. Ongoing clinical trials are anticipated to provide crucial insights into oligometastatic states, fostering the refinement of disease-specific oligometastatic state definitions and treatment algorithms. This article reviews existing data on the management of oligometastatic GI cancer, summarizes current state of knowledge for each disease state, and provides updates on ongoing studies in this space.

Outcomes From a Physician Health Center.

This retrospective cohort study describes the population of physicians seeking medical evaluation in a dedicated physician health center and identifies factors associated with needing practice restrictions. Participants had an initial evaluation between January 1, 2016, and December 31, 2022. We report personal and professional demographics and types of medical conditions in this cohort. An ordinal logistic regression analysis was used to identify factors associated with occupational outcomes. Physicians in a wide variety of specialties from 34 different states presented for evaluation of diverse medical problems. More than half of the participants presented with occupational concerns. The presence of a neurologic or psychiatric illness were the only factors associated with temporary or permanent restrictions. Physicians with medical conditions impacting their ability to practice have a professional obligation to obtain a thorough, objective medical evaluation. Such evaluations should support and protect patients, employers, and the physicians themselves.

Disruption of an ant-plant mutualism shapes interactions between lions and their primary prey.

Mutualisms often define ecosystems, but they are susceptible to human activities. Combining experiments, animal tracking, and mortality investigations, we show that the invasive big-headed ant (Pheidole megacephala) makes lions (Panthera leo) less effective at killing their primary prey, plains zebra (Equus quagga). Big-headed ants disrupted the mutualism between native ants (Crematogaster spp.) and the dominant whistling-thorn tree (Vachellia drepanolobium), rendering trees vulnerable to elephant (Loxodonta africana) browsing and resulting in landscapes with higher visibility. Although zebra kills were significantly less likely to occur in higher-visibility, invaded areas, lion numbers did not decline since the onset of the invasion, likely because of prey-switching to African buffalo (Syncerus caffer). We show that by controlling biophysical structure across landscapes, a tiny invader reconfigured predator-prey dynamics among iconic species.

Association of Neighborhood Disadvantage with Short- and Long-Term Outcomes After Pancreatectomy for Pancreatic Ductal Adenocarcinoma.

BACKGROUND: While lower socioeconomic status has been shown to correlate with worse outcomes in cancer care, data correlating neighborhood-level metrics with outcomes are scarce. We aim to explore the association between neighborhood disadvantage and both short- and long-term postoperative outcomes in patients undergoing pancreatectomy for pancreatic ductal adenocarcinoma (PDAC). PATIENTS AND METHODS: We retrospectively analyzed 243 patients who underwent resection for PDAC at a single institution between 1 January 2010 and 15 September 2021. To measure neighborhood disadvantage, the cohort was divided into tertiles by Area Deprivation Index (ADI). Short-term outcomes of interest were minor complications, major complications, unplanned readmission within 30 days, prolonged hospitalization, and delayed gastric emptying (DGE). The long-term outcome of interest was overall survival. Logistic regression was used to test short-term outcomes; Cox proportional hazards models and Kaplan-Meier method were used for long-term outcomes. RESULTS: The median ADI of the cohort was 49 (IQR 32-64.5). On adjusted analysis, the high-ADI group demonstrated greater odds of suffering a major complication (odds ratio [OR], 2.78; 95% confidence interval [CI], 1.26-6.40; p = 0.01) and of an unplanned readmission (OR, 3.09; 95% CI, 1.16-9.28; p = 0.03) compared with the low-ADI group. There were no significant differences between groups in the odds of minor complications, prolonged hospitalization, or DGE (all p > 0.05). High ADI did not confer an increased hazard of death (p = 0.63). CONCLUSIONS: We found that worse neighborhood disadvantage is associated with a higher risk of major complication and unplanned readmission after pancreatectomy for PDAC.

Corridor-based approach with spatial cross-validation reveals scale-dependent effects of geographic distance, human footprint and canopy cover on grizzly bear genetic connectivity.

Understanding how human infrastructure and other landscape attributes affect genetic differentiation in animals is an important step for identifying and maintaining dispersal corridors for these species. We built upon recent advances in the field of landscape genetics by using an individual-based and multiscale approach to predict landscape-level genetic connectivity for grizzly bears (Ursus arctos) across ~100,000 km2 in Canada's southern Rocky Mountains. We used a genetic dataset with 1156 unique individuals genotyped at nine microsatellite loci to identify landscape characteristics that influence grizzly bear gene flow at multiple spatial scales and map predicted genetic connectivity through a matrix of rugged terrain, large protected areas, highways and a growing human footprint. Our corridor-based modelling approach used a machine learning algorithm that objectively parameterized landscape resistance, incorporated spatial cross validation and variable selection and explicitly accounted for isolation by distance. This approach avoided overfitting, discarded variables that did not improve model performance across withheld test datasets and spatial predictive capacity compared to random cross-validation. We found that across all spatial scales, geographic distance explained more variation in genetic differentiation in grizzly bears than landscape variables. Human footprint inhibited connectivity across all spatial scales, while open canopies inhibited connectivity at the broadest spatial scale. Our results highlight the negative effect of human footprint on genetic connectivity, provide strong evidence for using spatial cross-validation in landscape genetics analyses and show that multiscale analyses provide additional information on how landscape variables affect genetic differentiation.

NBCe1-B/C-knockout mice exhibit an impaired respiratory response and an enhanced renal response to metabolic acidosis.

The sodium-bicarbonate cotransporter (NBCe1) has three primary variants: NBCe1-A, -B and -C. NBCe1-A is expressed in renal proximal tubules in the cortical labyrinth, where it is essential for reclaiming filtered bicarbonate, such that NBCe1-A knockout mice are congenitally acidemic. NBCe1-B and -C variants are expressed in chemosensitive regions of the brainstem, while NBCe1-B is also expressed in renal proximal tubules located in the outer medulla. Although mice lacking NBCe1-B/C (KOb/c) exhibit a normal plasma pH at baseline, the distribution of NBCe1-B/C indicates that these variants could play a role in both the rapid respiratory and slower renal responses to metabolic acidosis (MAc). Therefore, in this study we used an integrative physiologic approach to investigate the response of KOb/c mice to MAc. By means of unanesthetized whole-body plethysmography and blood-gas analysis, we demonstrate that the respiratory response to MAc (increase in minute volume, decrease in pCO2) is impaired in KOb/c mice leading to a greater severity of acidemia after 1 day of MAc. Despite this respiratory impairment, the recovery of plasma pH after 3-days of MAc remained intact in KOb/c mice. Using data gathered from mice housed in metabolic cages we demonstrate a greater elevation of renal ammonium excretion and greater downregulation of the ammonia recycling enzyme glutamine synthetase in KOb/c mice on day 2 of MAc, consistent with greater renal acid-excretion. We conclude that KOb/c mice are ultimately able to defend plasma pH during MAc, but that the integrated response is disturbed such that the burden of work shifts from the respiratory system to the kidneys, delaying the recovery of pH.

Polymerized human hemoglobin with low and high oxygen affinity in trauma models.

The present study aimed to compare the ability of tense (T) and relaxed (R) quaternary state polymerized human hemoglobin (PolyhHb) to restore hemodynamics after severe trauma in a rat model, and to assess their relative toxicity in a guinea pigs (GPs). To assess the efficacy of these PolyhHbs in restoring hemodynamics, Wistar rats were subjected to traumatic brain injury (TBI) followed by hemorrhagic shock (HS). Animals were separated into 3 groups based on the resuscitation solution: Whole blood, T-state or R-state PolyhHb, and followed for 2 hours after resuscitation. For toxicity evaluation, GPs were subjected to HS and the hypovolemic state was maintained for 50 minutes. Then, the GPs were divided randomly into 2 groups, and reperfused with T- or R-state PolyhHb. Rats resuscitated with blood and T-state PolyhHb had a higher recovery of MAP at 30 min after resuscitation when compared to R-state PolyhHb, demonstrating the greater ability of T-state PolyhHb to restore hemodynamics compared to R-state PolyhHb. Resuscitation with R-state PolyhHb in GPs increased markers of liver damage and inflammation, kidney injury and systemic inflammation compared to the T-state PolyhHb group. Finally, increased levels of cardiac damage markers, such as troponin were observed, indicating greater cardiac injury in GPs resuscitated with R-state PolyhHb. Therefore, our results showed that T-state PolyhHb exhibited superior efficacy in a model of TBI followed by HS in rats, and presented reduced vital organ toxicity in GPs, when compared to R-state PolyhHb.

Intravenous chloral hydrate anesthesia provides appropriate analgesia for surgical interventions in male Sprague-Dawley rats.

BACKGROUND: The use of chloral hydrate as a sole maintenance anesthetic agent in rodent research has been controversial due to statements made in reference literature conflicting with results of primary research studies regarding its analgesic efficacy, and because of its associated tissue damage when administered intraperitoneally. OBJECTIVE: Our aim was to assess the analgesic efficacy of chloral hydrate using an intravenous (i.v.) route of administration, in order to prevent the local tissue irritation or ileus that has been previously reported using intraperitoneal (i.p.) routes. METHODS: We measured tail withdrawal latencies to a nociceptive thermal stimulus (infrared beam) in Sprague-Dawley rats-first when awake (unanesthetized), and then subsequently during i.v. chloral hydrate anesthesia. During anesthesia we also measured ongoing heart and respiration rates. RESULTS: Withdrawal latencies during chloral hydrate anesthesia were significantly higher, and often maximal, indicating a robust analgesic effect. Importantly, both respiration and heart rate remained unchanged following exposure to the nociceptive stimulus, and were comparable to values observed under other anesthetics and during natural sleep. CONCLUSIONS: Together with previous studies, these results demonstrate that i.v. chloral hydrate provides excellent anesthetic depth and analgesic efficacy for surgical manipulations in rats.

Effects of Different Percentages of Blood Flow Restriction on Muscle Oxygen Saturation While Walking.

The purpose of this investigation was to determine the effect of different relative pressures of blood flow restriction (BFR) on muscle oxygen saturation (SmO2) while walking at 3.0 mph (4.83 kph). Fifteen physically active healthy adults performed seven 5-minute stages of walking at 3.0 mph with a blood flow restriction cuff applied to the proximal portion of the left or right leg while bilateral SmO2 changes were measured using near infra-red spectroscopy (NIRS) on the medial head of the gastrocnemius (GM) and vastus lateralis (VL) muscles. Other measurements including heart rate (HR), blood pressure (BP), rating of perceived exertion (RPE), and ground contact time balance (GCTB) were also collected. SmO2 measurements were analyzed using two-way repeated measures (RM) ANOVA while other measurements were analyzed using one-way RM ANOVA. We observed a significant main effect of LOP% (limb occlusion pressure) on the difference in total area of desaturation that occurred during each occlusion stage (ADS), p < 0.0001 η2 = .336, early ΔSmO2, p < 0.0001 in both the GAS η2 = .132 and VL η2 = .335. The results suggest that there are significant differences in SmO2 desaturation between 40%, 80%, and 100% LOP. Our findings suggest that incremental increases in LOP will bring about greater SmO2 desaturation during walking and may therefore induce a larger adaptive response on the muscles. However, increased LOP% may intensify perception of effort.

Braiding Indigenous rights and endangered species law.

Recovery targets fall short of culturally meaningful abundance.

Accuracy of models to prognosticate survival after surgery for pancreatic cancer in the era of neoadjuvant therapy.

BACKGROUND: Outcomes for pancreatic adenocarcinoma (PDAC) remain difficult to prognosticate. Multiple models attempt to predict survival following the resection of PDAC, but their utility in the neoadjuvant population is unknown. We aimed to assess their accuracy among patients that received neoadjuvant chemotherapy (NAC). METHODS: We performed a multi-institutional retrospective analysis of patients who received NAC and underwent resection of PDAC. Two prognostic systems were evaluated: the Memorial Sloan Kettering Cancer Center Pancreatic Adenocarcinoma Nomogram (MSKCCPAN) and the American Joint Committee on Cancer (AJCC) staging system. Discrimination between predicted and actual disease-specific survival was assessed using the Uno C-statistic and Kaplan-Meier method. Calibration of the MSKCCPAN was assessed using the Brier score. RESULTS: A total of 448 patients were included. There were 232 (51.8%) females, and the mean age was 64.1 years (±9.5). Most had AJCC Stage I or II disease (77.7%). For the MSKCCPAN, the Uno C-statistic at 12-, 24-, and 36-month time points was 0.62, 0.63, and 0.62, respectively. The AJCC system demonstrated similarly mediocre discrimination. The Brier score for the MSKCCPAN was 0.15 at 12 months, 0.26 at 24 months, and 0.30 at 36 months, demonstrating modest calibration. CONCLUSIONS: Current survival prediction models and staging systems for patients with PDAC undergoing resection after NAC have limited accuracy.

Elementary Overview of Heavy Metals.

BACKGROUND: Exposure to heavy metals is common as a result of environmental contamination of air, water, and soil as well as accumulation in food, tobacco, herbal medicines, and occupational contact. However, clinically relevant toxicity is much less prevalent. Toxic effects, when they occur, may present with non-specific symptoms, resulting in a very large differential for clinicians to consider. CONTENT: Arsenic, cadmium, lead, and mercury are four heavy metals with no biological role in humans. However, these metals are commonly used in industrial applications and consumer products. Since these elements are not biodegradeable, their potential toxic effects may be long-lasting within the environment. These heavy metals have the potential to accumulate in vital organs such as the brain, heart, and kidney where they may disrupt normal cellular functioning and if exposures are repetitive or of high concentration, toxicity may result. SUMMARY: The objective of this review is to provide an overview of arsenic, cadmium, lead, and mercury physical properties, common sources of exposure, basic toxicokinetics and health effects, and to review clinical guidelines and treatment strategies. Acute and chronic symptoms and recommended laboratory biomarker testing are also discussed.