Make It or Break It? Injury Impacts More Than Half of Deselected Athletes Who Dropped Out of the High-Performance Pathway System. A 4-Year Retrospective Cohort Study.

To investigate: (1) the injury epidemiology in an Australian academy; (2) how athletes transition through the high-performance sport (HPS) pathway; and (3) why athletes leave this HPS program. This retrospective cohort study was conducted at an Australian HPS academy over a 4-year period. Medical attention injuries were prospectively recorded. Injury incidence rates (IIR) and burden were calculated per 365 athlete-days, according to sport, sex, and pathway level. Athlete pathway levels were mapped to the Foundations, Talent, Elite, and Mastery (FTEM) framework. Reasons for athletes transitioning out were reported. Four hundred and eighty-one injuries were reported across 124 athletes at an IIR of 2.09 injuries per 365 athlete-days (95% CI = 1.91-2.29). Most athletes (103, 83.1%) were injured at least once over the 4-year period. IIRs increased (IRR = 1.17, 95% CI = 1.06-1.29, p = 0.001) as athletes progressed through the pathway. The most common reason for athlete attrition was deselection due to performance (n = 18), with 55.6% of these athletes sustaining an injury in the season prior to deselection. Injury burden was highest at E2 (119.5 days absence per 365 athlete-days (95% CI = 62.18-229.67)) and lowest at T4 (30.47 days absence per 365 athlete-days (95% CI = 21.98-42.24)). Injury occurrence is common across HPS, with IIRs increasing as athletes progressed to higher talent levels. Deselection due to poor performance was the main attrition factor, with more than half the deselected athletes impacted by injury prior to deselection. This study highlights an increased risk of deselection, following injury, and indicates the need for further development of prevention strategies targeting pathway athletes.

An early experience on the effect of solid organ transplant status on hospitalized COVID-19 patients.

We compared the outcome of COVID-19 in immunosuppressed solid organ transplant (SOT) patients to a transplant naïve population. In total, 10 356 adult hospital admissions for COVID-19 from March 1, 2020 to April 27, 2020 were analyzed. Data were collected on demographics, baseline clinical conditions, medications, immunosuppression, and COVID-19 course. Primary outcome was combined death or mechanical ventilation. We assessed the association between primary outcome and prognostic variables using bivariate and multivariate regression models. We also compared the primary endpoint in SOT patients to an age, gender, and comorbidity-matched control group. Bivariate analysis found transplant status, age, gender, race/ethnicity, body mass index, diabetes, hypertension, cardiovascular disease, COPD, and GFR <60 mL/min/1.73 m2 to be significant predictors of combined death or mechanical ventilation. After multivariate logistic regression analysis, SOT status had a trend toward significance (odds ratio [OR] 1.29; 95% CI 0.99-1.69, p = .06). Compared to an age, gender, and comorbidity-matched control group, SOT patients had a higher combined risk of death or mechanical ventilation (OR 1.34; 95% CI 1.03-1.74, p = .027).

Mitochondrial transplantation therapy for ischemia reperfusion injury: a systematic review of animal and human studies.

BACKGROUND: Mitochondria are essential organelles that provide energy for cellular functions, participate in cellular signaling and growth, and facilitate cell death. Based on their multifactorial roles, mitochondria are also critical in the progression of critical illnesses. Transplantation of mitochondria has been reported as a potential promising approach to treat critical illnesses, particularly ischemia reperfusion injury (IRI). However, a systematic review of the relevant literature has not been conducted to date. Here, we systematically reviewed the animal and human studies relevant to IRI to summarize the evidence for mitochondrial transplantation. METHODS: We searched MEDLINE, the Cochrane library, and Embase and performed a systematic review of mitochondrial transplantation for IRI in both preclinical and clinical studies. We developed a search strategy using a combination of keywords and Medical Subject Heading/Emtree terms. Studies including cell-mediated transfer of mitochondria as a transfer method were excluded. Data were extracted to a tailored template, and data synthesis was descriptive because the data were not suitable for meta-analysis. RESULTS: Overall, we identified 20 animal studies and two human studies. Among animal studies, 14 (70%) studies focused on either brain or heart IRI. Both autograft and allograft mitochondrial transplantation were used in 17 (85%) animal studies. The designs of the animal studies were heterogeneous in terms of the route of administration, timing of transplantation, and dosage used. Twelve (60%) studies were performed in a blinded manner. All animal studies reported that mitochondrial transplantation markedly mitigated IRI in the target tissues, but there was variation in biological biomarkers and pathological changes. The human studies were conducted with a single-arm, unblinded design, in which autologous mitochondrial transplantation was applied to pediatric patients who required extracorporeal membrane oxygenation (ECMO) for IRI-associated myocardial dysfunction after cardiac surgery. CONCLUSION: The evidence gathered from our systematic review supports the potential beneficial effects of mitochondrial transplantation after IRI, but its clinical translation remains limited. Further investigations are thus required to explore the mechanisms of action and patient outcomes in critical settings after mitochondrial transplantation. Systematic review registration The study was registered at UMIN under the registration number UMIN000043347.

Successes, challenges and needs regarding rural health medical education in continental Central America: a literature review and narrative synthesis.

INTRODUCTION: Central American countries, like many others, face a shortage of rural health physicians. Most medical schools in this region are located in urban areas and focus on tertiary care training rather than on community health or primary care, which are better suited for rural practice. However, many countries require young physicians to do community service in rural communities to address healthcare provider shortages. This study aimed to: (a) synthesize what is known about the current state of medical education preparing physicians for rural practice in this region, and (b) identify common needs, challenges and opportunities for improving medical education in this area. METHODS: A comprehensive literature review was conducted between December 2013 and May 2014. The stepwise, reproducible search process included English and Spanish language resources from both data-based web search engines (PubMed, Web of Science/Web of Knowledge, ERIC and Google Scholar) and the grey literature. Search criteria included MeSH terms: 'medical education', 'rural health', 'primary care', 'community medicine', 'social service', in conjunction with 'Central America', 'Latin America', 'Mexico', 'Guatemala', 'Belize', 'El Salvador', 'Nicaragua', 'Honduras', 'Costa Rica' and 'Panama'. Articles were included in the review if they (1) were published after 1984; (2) focused on medical education for rural health, primary care, community health; and (3) involved the countries of interest. A narrative synthesis of the content of resources meeting inclusion criteria was done using qualitative research methods to identify common themes pertaining to the study goals. RESULTS: The search revealed 20 resources that met inclusion criteria. Only four of the 20 were research articles; therefore, information about this subject was primarily derived from expert opinion. Thematic analysis revealed the historical existence of several innovative programs that directly address rural medicine training needs, suggesting that expertise is present in this region. However, numerous challenges limit sustainability or expansion of successful programs. Common challenges include: (a) physicians' exposure to rural medicine primarily takes place during social service commitment time, rather than during formal medical training; (b) innovative educational programs are often not sustainable due to financial and leadership challenges; (c) the majority of physician manpower is in urban areas, resulting in few rural physician role models and teachers; and (d) there is insufficient collaboration to establish clinical and educational systems to meet rural health needs. Recurring suggestions for curricular changes include: (a) making primary care training a core component of medical school education; and (b) expanding medical school curricula in cross-cultural communication and social determinants of disease. Suggestions for health system changes include: (a) improving living and working conditions for rural physicians; and (b) establishing partnerships between educational, governmental and non-governmental organizations and rural community leadership, to promote rural health training and systems. CONCLUSIONS: Expertise in rural medicine and training exists in continental Central America. However, there are numerous challenges to improving medical education to meet the needs of rural communities. Overcoming these challenges will require creative solutions, new partnerships, and evaluation and dissemination of successful educational programs. There is a great need for further research on this topic.

Gender and socioecological level differences in stakeholders' perceptions of athlete attrition factors in an Australian high-performance pathway system.

OBJECTIVES: This study aimed to build on previous work by the authors. It examines how socioecological level and gender influence high-performance sport system (HPSS) stakeholders' perspectives of the relative importance and feasibility to address athlete attrition factors within an Australian high-performance pathway system (HPPS). DESIGN: Mixed methods. METHODS: Sub-analysis was conducted of rating data from 30 participants who had contributed to identifying 83 statements in 13 clusters in a previous Concept Mapping study. The 13 clusters were statistically analysed in 'R' using cumulative link mixed models (CLMMs) to determine differences in perceived importance and feasibility between 1) socioecological levels, and 2) genders. RESULTS: Mean ratings for 11 and three of the 13 clusters were statistically significantly different between at least two of the five socioecological levels, for importance and feasibility, respectively. Athletes had the largest variation in mean ratings from the most (athlete health 4.59), to least (performance potential 2.83) important cluster, when compared to the other four socioecological levels. There were statistically significant differences between the ratings between genders (Men/Women) for two clusters for each rating scale: Importance: 'athlete health' (M3.33:W3.84 [p 0.012]); 'performance potential' (M3.35:W2.57; [p 0.001]), Feasibility: 'abuse and mismanagement of health' (M2.97:W3.68; [p 0.000]) and 'athlete health' (M2.54:W3.33; [p 0.000]). CONCLUSIONS: This study highlights the need to implement more robust athlete attrition monitoring protocols. It also highlights the importance of listening to youth athletes' voices, and enabling equal gender representation to ensure holistically tailored environments are created to retain talented athletes in high-performance pathway programmes.

Injury and illness in short-course triathletes: A systematic review.

BACKGROUND: Determining the incidence and prevalence of injury and illness in short-course triathletes would improve understanding of their etiologies and therefore assist in the development and implementation of prevention strategies. This study synthesizes the existing evidence on the incidence and prevalence of injury and illness and summarizes reported injury or illness etiology and risk factors affecting short-course triathletes. METHODS: This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies reporting health problems (injury and illness) in triathletes (all sexes, ages, and experience levels) training and/or competing in short-course distances were included. Six electronic databases (Cochrane Central Register of Controlled Trials, MEDLINE, Embase, APA PsychINFO, Web of Science Core Collection, and SPORTDiscus) were searched. Risk of bias was independently assessed by 2 reviewers using the Newcastle-Ottawa Quality Assessment Scale. Two authors independently completed data extraction. RESULTS: The search yielded 7998 studies, with 42 studies eligible for inclusion. Twenty-three studies investigated injuries, 24 studies investigated illnesses, and 5 studies investigated both injuries and illnesses. The injury incidence rate ranged 15.7-24.3 per 1000 athlete exposures, and the illness incidence rate ranged 1.8-13.1 per 1000 athlete days. Injury and illness prevalence ranged between 2%-15% and 6%-84%, respectively. Most injuries reported occurred during running (45%-92%), and the most frequently reported illnesses affected the gastrointestinal (7%-70%), cardiovascular (14%-59%), and respiratory systems (5%-60%). CONCLUSION: The most frequently reported health problems in short-course triathletes were: overuse and lower limb injuries associated with running; gastrointestinal illnesses and altered cardiac function, primarily attributable to environmental factors; and respiratory illness mostly caused by infection.

Differential Mitochondrial Bioenergetics in Neurons and Astrocytes Following Ischemia-Reperfusion Injury and Hypothermia.

The close interaction between neurons and astrocytes has been extensively studied. However, the specific behavior of these cells after ischemia-reperfusion injury and hypothermia remains poorly characterized. A growing body of evidence suggests that mitochondria function and putative transference between neurons and astrocytes may play a fundamental role in adaptive and homeostatic responses after systemic insults such as cardiac arrest, which highlights the importance of a better understanding of how neurons and astrocytes behave individually in these settings. Brain injury is one of the most important challenges in post-cardiac arrest syndrome, and therapeutic hypothermia remains the single, gold standard treatment for neuroprotection after cardiac arrest. In our study, we modeled ischemia-reperfusion injury by using in vitro enhanced oxygen-glucose deprivation and reperfusion (eOGD-R) and subsequent hypothermia (HPT) (31.5 °C) to cell lines of neurons (HT-22) and astrocytes (C8-D1A) with/without hypothermia. Using cell lysis (LDH; lactate dehydrogenase) as a measure of membrane integrity and cell viability, we found that neurons were more susceptible to eOGD-R when compared with astrocytes. However, they benefited significantly from HPT, while the HPT effect after eOGD-R on astrocytes was negligible. Similarly, eOGD-R caused a more significant reduction in adenosine triphosphate (ATP) in neurons than astrocytes, and the ATP-enhancing effects from HPT were more prominent in neurons than astrocytes. In both neurons and astrocytes, measurement of reactive oxygen species (ROS) revealed higher ROS output following eOGD-R, with a non-significant trend of differential reduction observed in neurons. HPT after eOGD-R effectively downregulated ROS in both cells; however, the effect was significantly more effective in neurons. Lipid peroxidation was higher after eOGD-R in neurons, while in astrocytes, the increase was not statistically significant. Interestingly, HPT had similar effects on the reduction in lipoperoxidation after eOGD-R with both types of cells. While glutathione (GSH) levels were downregulated after eOGD-R in both cells, HPT enhanced GSH in astrocytes, but worsened GSH in neurons. In conclusion, neuron and astrocyte cultures respond differently to eOGD-R and eOGD-R + HTP treatments. Neurons showed higher sensitivity to ischemia-reperfusion insults than astrocytes; however, they benefited more from HPT therapy. These data suggest that given the differential effects from HPT in neurons and astrocytes, future therapeutic developments could potentially enhance HPT outcomes by means of neuronal and astrocytic targeted therapies.

RKIP phosphorylation and STAT3 activation is inhibited by oxaliplatin and camptothecin and are associated with poor prognosis in stage II colon cancer patients.

BACKGROUND: A major obstacle in treating colorectal cancer (CRC) is the acquired resistance to chemotherapeutic agents. An important protein in the regulation of cancer cell death and clinical outcome is Raf kinase inhibitor protein (RKIP). In contrast, activated signal transducer and activator of transcription 3 (STAT3) is a protein that promotes tumor cell survival by inhibiting apoptosis and has an important role in cancer progression in many of cancer types. The aim of this study was to evaluate the regulation of RKIP and STAT3 after treatment with clinically relevant chemotherapeutic agents (camptothecin (CPT) and oxaliplatin (OXP)) and the cytokine interleukin-6 (IL-6) in HCT116 colon cancer cells as well as evaluate the association between RKIP and STAT3 with clinical outcome of Stage II colon cancer patients. METHODS: HCT-116 colon cancer cells were treated with CPT, OXP, and IL-6 separately or in combination in a time and dose-dependent manner and examined for phosphorylated and non-phosphorylated RKIP and STAT3 via Western blot analysis. STAT3 transcriptional activity was measured via a luciferase reporter assay in HCT116 cells treated with CPT, IL-6 or transfected with JAK 1, 2 separately or in combination. We extended these observations and determined STAT3 and RKIP/ pRKIP in tumor microarrays (TMA) in stage II colon cancer patients. RESULTS: We demonstrate IL-6-mediated activation of STAT3 occurs in conjunction with the phosphorylation of RKIP in vitro in human colon cancer cells. OXP and CPT block IL-6 mediated STAT3 activation and RKIP phosphorylation via the inhibition of the interaction of STAT3 with gp130. We determined that STAT3 and nuclear pRKIP are significantly associated with poor patient prognosis in stage II colon cancer patients. CONCLUSIONS: In the analysis of tumor samples from stage II colon cancer patients and the human colon carcinoma cell line HCT116, pRKIP and STAT3, 2 proteins potentially involved in the resistance to conventional treatments were detected. The phosphorylation of pRKIP and STAT3 are induced by the cytokine IL-6 and suppressed by the chemotherapeutic drugs CPT and OXP. Therefore, these results suggest that STAT3 and pRKIP may serve as prognostic biomarkers in stage II colon cancer patients and may improve chemotherapy.

Intracranial Hypertension following Acute Mesenteric Ischemia: A Case Study on the Multiple Compartment Syndrome.

In this case study, we describe a 25-year-old male who was admitted due to a severe traumatic brain injury, requiring invasive intracranial pressure monitoring. At 48 hours posttrauma, he developed intracranial hypertension refractory to medical treatment without tomographic changes in the brain. Subsequently, intra-abdominal hypertension and tomographic signs of abdominal surgical pathology were observed. An exploratory laparotomy was performed with an intraoperative diagnosis of acute mesenteric ischemia. After surgical intervention for the abdominal pathology, intracranial pressure was restored to physiological values with a favorable recovery of the patient. In this report, the relationship between intracranial pressure and intra-abdominal pressure is discussed, highlighting the delicate association between the brain, abdomen, and thorax. Measures should be taken to avoid increases in intra-abdominal pressure in neurocritical patients. When treating intracranial hypertension refractory to conventional measures, abdominal causes and multiple compartment syndrome must be considered. The cranial compartment has physiological interdependence with other body compartments, where one can be modified by variations from another, giving rise to the concept of multiple compartment syndrome. Understanding this relationship is fundamental for a comprehensive approach of the neurocritical patient. To the best of our knowledge, this is the first report of a comatose patient post-traumatic brain injury, who developed medically unresponsive intracranial hypertension secondary to acute mesenteric ischemia, in which surgical resolution of intra-abdominal pathology resulted in intracranial pressure normalization and restitutio ad integrum of neurological status.

Life-Threatening Hematuria as Initial Presentation of a Complicated Transplant Renal Artery Pseudoaneurysm.

In this case report, we describe the clinical course of a complicated transplant renal artery (TRA) pseudoaneurysm, clinically featured by gross and massive hematuria one month after a kidney transplant was performed on a 50 year-old male patient. TRA pseudoaneurysm is a rare but potentially life-threatening complication that may result in bleeding, infection, graft dysfunction/loss, lower limb ischemia/loss, hemorrhagic shock, and death. TRA pseudoaneurysm treatment remains challenging as it needs to be tailored to the patient characteristics including hemodynamic stability, graft function, anatomy, presentation, and pseudoaneurysm features. This publication discusses the clinical scenario of massive gross hematuria that derived from a retroperitoneal hematoma which originated from an actively bleeding TRA pseudoaneurysm. This case highlights the combined approach of endovascular stent placement and subsequent transplant nephrectomy as a last resort in the management of intractable bleeding from a complicated TRA pseudoaneurysm. To the best of our knowledge, this is the first published case report of an actively bleeding TRA anastomotic pseudoaneurysm that caused a massive retroperitoneal bleed that in turn evacuated via the bladder after disrupting the ureter-to-bladder anastomosis. A temporizing hemostatic arterial stent placed percutaneously allowed for a safer and controlled emergency transplant nephrectomy.

External Stenting (Exostenting) to Correct Vascular Torsion and Angulation.

Organ transplantation can be associated with vascular torsions and angulations of both recipient and donor vessels. Such kinks and/or torsions of vessels can compromise the vascular integrity, obstruct inflow and/or outflow, and result in loss of the organ and/or body parts. On many occasions, mild angulations and torsions can be successfully addressed by repositioning the organ. In cases where the abnormal findings persist, maneuvers such as placing a fat pad to create a smoother curve, or even opening the peritoneum (in the case of kidney transplants) to allow for a better positioning of the organ, are associated with successful outcomes. When such torsions/angulations persist despite these approaches, further innovative tactics are required. In the current report, we propose a technique that involves longitudinally opening of a synthetic graft that is rigid enough to maintain its shape, such as a ringed polytetrafluoroethylene graft, and placing it as an external stent around the angulated/torsioned vessel. This maneuver will correct the underlying vascular compromise without having to perform any further invasive interventions, such as reimplanting the organ or resecting part of the involved vessel. Although primarily illustrated for application by describing an instance in which exostenting was applied during kidney transplantation, our approach could be applied to any vessel under many circumstances where angulations/twists are encountered. In this report, we describe the use of an external stent, also called exostenting, to correct a severe torsion/angulation of the external iliac artery in a kidney transplant recipient where all other measures were unsuccessful.

COVID-19-Associated Portal Vein Thrombosis Post-Cholecystitis.

This case study describes a 45-year-old Caucasian male with a past medical history of obesity, hypertension, and non-insulin-dependent diabetes mellitus, who in the setting of coronavirus disease 2019 (COVID-19) pneumonia, developed portal vein thrombosis (PVT) presenting as an acute abdomen after hospital discharge from a cholecystitis episode. PVT is a very infrequent thromboembolic condition, classically occurring in patients with systemic conditions such as cirrhosis, malignancy, pancreatitis, diverticulitis, autoimmunity, and thrombophilia. PVT can cause serious complications, such as intestinal infarction, or even death, if not promptly treated. Due to the limited number of reports in the literature describing PVT in the COVID-19 setting, its prevalence, natural history, mechanism, and precise clinical features remain unknown. Therefore, clinical suspicion should be high for PVT, in any COVID-19 patient who presents with abdominal pain or associated signs and symptoms. To the best of our knowledge, this is the first report of COVID-19-associated PVT causing extensive thrombosis in the portal vein and its right branch, occurring in the setting of early-stage cirrhosis after a preceding episode of cholecystitis.

What Contributes to Athlete Performance Health? A Concept Mapping Approach.

BACKGROUND: In high-performance sport, athlete performance health encompasses a state of optimal physical, mental, and social wellbeing related to an athlete's sporting success. The aim of this study was to identify the priority areas for achieving athlete performance health in Australia's high-performance sport system (HPSS). METHODS: Participants across five socioecological levels of Australia's HPSS were invited to contribute to this study. Concept mapping, a mixed-methods approach incorporating qualitative and quantitative data collection, was used. Participants brainstormed ideas for what athlete performance health requires, sorted the ideas into groups based on similar meaning and rated the importance, and ease of achieving each idea on a scale from 1 (not important/easiest to overcome) to 5 (extremely important/hardest to overcome). RESULTS: Forty-nine participants generated 97 unique statements that were grouped into 12 clusters following multidimensional scaling and hierarchical cluster analysis. The three clusters with highest mean importance rating were (mean importance rating (1-5), mean ease of overcoming (1-5)): 'Behavioral competency' (4.37, 2.30); 'Collaboration and teamwork' (4.19, 2.65); 'Valuing athlete wellbeing' (4.17, 2.77). The 12 clusters were grouped into five overarching domains: Domain one-Performance health culture; Domain two-Integrated strategy; Domain three-Operational effectiveness; Domain four-Skilled people; Domain five-Leadership. CONCLUSION: A diverse sample of key stakeholders from Australia's HPSS identified five overarching domains that contribute to athlete performance health. The themes that need to be addressed in a strategy to achieve athlete performance health in Australia's HPSS are 'Leadership', 'Skilled people', 'Performance health culture', 'Operational effectiveness', and 'Integrated strategy'.

Cardiac arrest associated with non-toxigenic corynebacterium diphtheria strain: A case report.

Here we document a rare, acute, infection caused by non-toxigenic Corynebacterium diphtheriae and the resulting unique and severe clinical sequelae. Our patient was a young man with no known pre-existing conditions that presented in cardiopulmonary arrest. We contrast this case with prior instances of non-toxigenic C. diphtheriae strain infection in the United States and summarize the literature that suggests systemic infection can result in cardiogenic toxicity. We speculate on a possible missed, pre-existing condition that could have increased this patient's susceptibility to poor clinical outcome.

Stakeholder insights into athlete attrition in the high-performance pathway.

OBJECTIVES: Primary: To gain a system-wide perspective on factors leading to athlete attrition from a high-performance sport system (HPSS). Secondary: To identify what a sample of system-wide stakeholders and past athletes value as the most important and feasible attrition factors to address to retain talented athletes. DESIGN: Mixed-methods. METHODS: Concept mapping was used for qualitative data collection and quantitative data analysis. Sixty-one participants including: (i) past athletes from an Australian state sporting institute; (ii) their families; and (iii) internal and external stakeholders to a HPSS who supported past athletes. RESULTS: Participants brainstormed 83 unique statements (i.e. attrition factors) that were mapped into 13 clusters of attrition factors following multidimensional scaling and hierarchical cluster analysis performed on the participants sorting data: 'abuse and mismanagement of health'; 'athlete health'; 'limited support/resourcing'; 'coaching'; 'inconsistent processes'; 'financial and career support'; 'pathway structure'; 'organisational dynamics'; 'competitive stress'; 'performance potential'; 'challenges with selection and transition'; 'psychological state'; and 'competing non-sport priorities'. 'Abuse and mismanagement of health' had the highest mean importance (3.76 out of 5) and feasibility (3.31) rating. The 13 clusters were further grouped into four overarching domains: 'sport system policy, structure and processes'; 'pathway structure, transition and support'; 'individual athlete health and capability'; and 'whole-of-life demands and priorities'. The domain 'sport system policy, structure and processes' contained the most important and feasible clusters. CONCLUSIONS: Macro (system-level) and micro (intrapersonal and interpersonal) level athlete attrition factors should be considered together. Athlete health was considered the most important athlete retention issue to address.

The Fanconi anemia pathway and Breast Cancer: A comprehensive review of clinical data.

The development of breast cancer depends on several risk factors, including environmental, lifestyle and genetic factors. Despite the evolution of DNA sequencing techniques and biomarker detection, the epidemiology and mechanisms of various breast cancer susceptibility genes have not been elucidated yet. Dysregulation of the DNA damage response causes genomic instability and increases the rate of mutagenesis and the risk of carcinogenesis. The Fanconi Anemia (FA) pathway is an important component of the DNA damage response and plays a critical role in the repair of DNA interstrand crosslinks and genomic stability. The FA pathway involves 22 recognized genes and specific mutations have been identified as the underlying defect in the majority of FA patients. A thorough understanding of the function and epidemiology of these genes in breast cancer is critical for the development and implementation of individualized therapies that target unique tumor profiles. Targeted therapies (PARP inhibitors) exploiting the FA pathway gene defects have been developed and have shown promising results. This narrative review summarizes the current literature on the involvement of FA genes in sporadic and familial breast cancer with a focus on clinical data derived from large cohorts.

Transplant Renal Artery Stenosis Revascularization: Common Distal External Iliac Bypass.

Stenosis proximal to transplant renal artery anastomoses are complications leading to allograft dysfunction. This study was aimed to evaluate a novel surgical approach to renal allograft revascularization, taking into consideration the length of time elapsed since transplantation. We describe an arterial bypass using a polytetrafluoroethylene (PTFE) graft from the common iliac artery (proximal to the renal artery implantation) to the external iliac artery (distal to the renal artery implantation) that allows the adequate revascularization of both the transplant kidney, as well as the lower extremity. This technique provides several advantages when compared with previously described procedures to revascularize a transplanted kidney with an iliac artery stenosis proximal to the allograft implantation site. Benefits of this technique include (1) no need to repair the stenosis, (2) no need to take down and redo the arterial anastomosis, (3) no need to perform a dissection around the renal hilum of the transplanted kidney, (4) no requirement to address the anastomosis transfer, and (5) no need to perfuse the kidney with preservation fluid at the time of repair and/or (6) avoidance of potential injury to the renal parenchyma and/or hilum during dissections. Adequate perfusion of the organ, as well as of the lower extremity was verified by serial Doppler duplex ultrasound evaluations. Hence, we describe a novel revascularization technique in instances of kidney transplant and lower extremity ischemia.

Renal Transplant Artery Inflow Stenosis Treated with Femorofemoral Bypass.

In this case report we describe a novel and successful revascularization approach in instances of allograft and distal limb ischemia after kidney transplantation. Stenosis proximal to transplant renal artery anastomoses is a complication leading to allograft dysfunction and/or loss. We present a femorofemoral bypass graft with ringed polytetrafluoroethylene (PTFE). In this occasion, revascularization was achieved by a backflow mechanism. The approach described achieved its goal of revascularizing the allograft as well as the distal extremity, with both short- and long-term successful outcomes. Benefits of this approach when compared with re-implantation or procedures directly involving the transplant renal artery include minimization of ischemic time, no need to repair the stenosis, anastomoses with vessels of greater diameter, no need to perfuse the kidney, no need to take down the renal artery anastomosis, no need to dissect the transplanted kidney, and no further lower extremity ischemia. This approach does not require any proximal temporary inflow occlusion (as seen with stent placement) or clamping of the arterial inflow to the kidney. This procedure was completed without having to infuse any preservation fluid into the kidney.

Diagnostic Dilemma of Paraneoplastic Rheumatic Disorders: Case Series and Narrative Review.

Paraneoplastic rheumatic disorder (RD) is a disorder that may present before, concurrent with, or after the diagnosis of malignancy. Paraneoplastic RDs are a clinical expression of occult cancer that is not directly related to a tumor or metastasis and manifests as rheumatoid symptoms. The RD is determined by the organ system affected by articular, muscular, cutaneous, vascular, or miscellaneous symptoms. Each case is challenging to diagnose because cancer may present with similar symptoms as a common rheumatic disorder. Of note, the majority of cases have minimal responsiveness or no responsiveness to standard rheumatoid treatment. Therefore, it is imperative to recognize and treat the underlying cancer accordingly. Herein, we present four different diagnostic dilemma cases of RD: case #1 - leukocytoclastic vasculitis and C3 glomerulopathy, case #2 - scleroderma, case #3 - Raynaud's syndrome and possible lupus-like syndrome, and case #4 - inflammatory myositis. Institutional IRB approval was obtained for this case series. We will discuss and review the literature on each topic. In addition, we will mention a review of paraneoplastic rheumatoid arthritis. As rheumatic disease is associated with the use of immune checkpoint inhibitors (ICIs) for cancer treatment, we will briefly discuss some of the most common rheumatic presentations in the setting of these drugs. This case review aims to inform clinicians about the atypical presentation of paraneoplastic RD and to highlight the need for interdisciplinary management between rheumatologists, oncologists, and primary care practitioners.

Bilateral Spontaneous Pneumothorax in a COVID-19 and HIV-Positive Patient: A Case Report.

This case report describes a 60 year-old Black-American male with a past medical history of human immunodeficiency virus (HIV) infection and hyperthyroidism, who suffered a bilateral spontaneous pneumothorax (SP) in the setting of coronavirus disease 2019 (COVID-19) pneumonia. SP is a well-established complication in HIV-positive patients and only recently has been associated with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. While HIV and COVID-19 infections have been independently linked with increased risk of SP development, it is unknown if both infections interact in a synergistic fashion to exacerbate SP risk. According to the Centers for Disease Control and Prevention (CDC), patients living with HIV have a higher risk of developing severe COVID-19 infection and the mechanism remains to be elucidated. To the best of our knowledge, this is the first report of a HIV-positive patient, who in the setting of SARS-CoV-2 infection, developed bilateral apical spontaneous pneumothorax and was later found to have a left lower lobe tension pneumothorax. This case highlights the importance of considering SP on the differential diagnosis when HIV-positive patients suddenly develop respiratory distress in the setting of SARS-CoV-2 infection.