The Role of Demographic and Clinical Factors in Germline Mutation Testing for Patients with Primary Hyperparathyroidism.

INTRODUCTION: Guidelines recommending genetic counseling in primary hyperparathyroidism (PHPT) vary. To further delineate current recommendations, this study examined genetic counseling referral patterns and rates of mutations in surgical patients with PHPT. PATIENTS AND METHODS: A single-institution review was performed of adult patients who underwent parathyroidectomy for presumed sporadic PHPT. Genetic testing indications of hypercalcemia onset ≤ 40 years, multigland disease (MGD), family history (FHx) of PHPT, or other clinical indications suspicious for a PHPT-related endocrinopathy were examined by demographics and mutation detection rates. RESULTS: Genetic counseling was performed in 237 (37.9%) of 625 patients. Counseling was discussed but not performed in 121 (19.4%) patients. No evidence was noted of genetic referral discussion in the remaining 267 (42.7%). Of these groups, patients who received genetic counseling were youngest, p < 0.001 [median age 55.3 (IQR 43.2, 66.7) years]. The majority of patients with indications of age ≤ 40 years (65.7%), FHx (78.0%), and other clinical indications (70.7%) underwent genetic counseling, while most with MGD (57.0%) did not. Eight mutations were detected in 227 patients (3.5%). Mutations included: MEN1 (n = 2), CDC-73 (n = 4), and CASR (n = 2). Detection was most common in patients with FHx (4/71, 5.6%), then age ≤ 40 years (3/66, 4.5%), and other clinical indications (3/80, 3.8%). No mutations were identified in 48 patients tested solely for MGD. CONCLUSIONS: Most patients with onset of hypercalcemia age ≤ 40 years, positive FHx, or other clinical concerns underwent genetic counseling, while most with MGD did not. As no germline mutations were identified in patients with MGD alone, further investigation of MGD as a sole indication for genetic counseling may be warranted.

Phenotypes of primary hyperparathyroidism: Does parathyroidectomy improve clinical outcomes for all?

BACKGROUND: Primary hyperparathyroidism consists of 3 biochemical phenotypes: classic, normocalcemic, and normohormonal primary hyperparathyroidism. The clinical outcomes of patients with normocalcemic primary hyperparathyroidism and normohormonal primary hyperparathyroidism are not well described. METHOD: A retrospective review of patients who underwent parathyroidectomy at a single institution was performed. A logistical regression analysis of postoperative nephrolithiasis and highest percentage change in dual-energy x-ray absorptiometry scan comparison using Kruskal-Wallis test and Cox proportional hazard analysis of recurrence-free survival were performed. RESULTS: A total of 421 patients were included (340 classic, 39 normocalcemic primary hyperparathyroidism, 42 normohormonal primary hyperparathyroidism). Median follow-up was 8.8 months (range 0-126). Higher rates of multigland disease were seen in normocalcemic primary hyperparathyroidism (64.1%) and normohormonal primary hyperparathyroidism (56.1%) compared to the classic (25.8%), P < .001. There were no differences in postoperative complications. The largest percentage increases in bone mineral density at the first postoperative dual-energy x-ray absorptiometry scan were higher for classic (mean ± SD, 6.4 ± 9.1) and normocalcemic primary hyperparathyroidism (4.8 ± 11.9) compared to normohormonal primary hyperparathyroidism, which remained stable (0.2 ± 14.2). Normocalcemic primary hyperparathyroidism were more likely to experience nephrolithiasis postoperatively, 6/13 (46.2%) compared to 11/68 (16.2%) classic, and 2/13 (15.4%) normohormonal primary hyperparathyroidism, P = .0429. Normocalcemic primary hyperparathyroidism was the only univariate predictor of postoperative nephrolithiasis recurrence (odds ratio [95% confidence interval] 4.44 [1.25-15.77], P = .029). Normocalcemic primary hyperparathyroidism was significantly associated with persistent disease with 6/32 (18.8%) compared to 1/36 (2.8%) and 3/252 (1.2%) in normohormonal primary hyperparathyroidism and classic (P < .001). CONCLUSION: Three phenotypes of primary hyperparathyroidism are distinct clinical entities. Normocalcemic primary hyperparathyroidism had higher incidence of persistent disease and postoperative nephrolithiasis but demonstrated improvements in postoperative bone density. These data should inform preoperative discussions with patients with normocalcemic primary hyperparathyroidism and normohormonal primary hyperparathyroidism regarding postoperative expectations.

Parathyroidectomy in the elderly is beneficial and safe with similar improvements in postoperative bone mineral density.

BACKGROUND: This study evaluated bone health outcomes of parathyroidectomy in elderly primary hyperparathyroidism (pHPT) patients. METHODS: A retrospective review was performed of parathyroidectomy patients with pHPT at a single institution from 2010 to 2019. Bone mineral density (BMD) improvements at postoperative dual-energy X-ray absorptiometry (DEXA) scans were analyzed between groups aged ≥75 and < 75 years using 1:1 matching on preoperative BMD. RESULTS: Patients ≥75 had BMD improvements through the second postoperative DEXA scans. While mean T-scores slightly improved in the ≥75 group during the study period, T-score improvement was more significant in the <75 group at first and third postoperative DEXA scans with +0.7 < 75 and +0.1 improvements ≥75 by the third DEXA (p = 0.026). Postoperative fragility fracture rates were similar in the ≥75 group, but significantly improved in patients <75 (10.4% preoperatively to 1.4% postoperatively, p = 0.020). Both cohorts had low complication rates with recurrent laryngeal nerve injury and permanent hypocalcemia of <1% (p = 0.316). CONCLUSIONS: Postoperative BMD improvement was similar between the two cohorts with no difference in complication rates suggesting parathyroidectomy is safe and effective in the elderly.

Making an informed choice: Which breast reconstruction type has the lowest complication rate?

INTRODUCTION: The aim of this study was to investigate long-term breast reconstruction outcomes at a single institution in order to offer data-driven counseling for patients. METHODS: A retrospective review was performed of 399 patients who underwent mastectomy with 1-stage implant-based breast reconstruction (IBBR), 2-stage IBBR, or autologous tissue reconstruction (ATR) for invasive breast cancer or ductal carcinoma in situ at our institution from 2010 to 2017. Complications were classified as major for any unplanned return to the operating room (OR). RESULTS: Overall complication rates were similar among 1-stage IBBR (59%), 2-stage IBBR (60%), and ATR (52%, p = 0.54). Factors independently associated with major complications were diabetes (OR = 25.4 95% CI: 3.2-202.4; p = 0.002), and 1-stage IBBR vs. ATR (1-stage: OR = 2.0 95% CI: 1.0-4.0; p = 0.04). Bilateral procedures were also at increased risk of major complications on univariate analysis (OR = 1.59 95% CI: 1.0-2.5; p = 0.04). CONCLUSIONS: Long-term breast reconstruction complication rates are higher than previously anticipated. Patients should be counseled that IBBR is associated with higher rates of complications, including unplanned return to the OR, compared to ATR.

The diagnostic value of splenectomy in patients without a definitive preoperative diagnosis.

BACKGROUND: The purpose of this study was to describe the diagnostic value and therapeutic benefit of diagnostic splenectomy. METHODS: Retrospective review was performed of patients undergoing splenectomy with an unknown diagnosis (UD), a hematologic malignancy (HM) or idiopathic thrombocytopenic purpura. Surgical indications and postoperative outcomes were evaluated. RESULTS: 113 splenectomy patients were identified. Of the UD patients undergoing splenectomy, 46% (n = 16) received a definitive diagnosis postoperatively. A change in diagnosis occurred in 12% (n = 4) of HM patients. Complete symptom relief was observed more often in UD patients who received a definitive diagnosis after splenectomy 69% (n = 11), compared to the 47% (n = 9) who did not receive definitive diagnosis postoperatively. CONCLUSIONS: The diagnostic ability of splenectomy was 46% when the diagnosis was unknown preoperatively. Additionally, a majority of patients experienced relief of symptoms postoperatively. Splenectomy may be a useful diagnostic and therapeutic tool in select UD and HM patients.

Primary Colorectal Lymphoma: Institutional Experience and Review of a National Database.

BACKGROUND: Primary colorectal lymphoma is rare, representing 0.2% to 0.6% of all colorectal cancers. Because of its low incidence and histologic variety, no treatment guidelines exist. OBJECTIVE: The purpose was to report the experience of primary colorectal lymphoma in an institutional and a national cohort. DESIGN: This was a retrospective cohort study. SETTINGS: The study was conducted with institutional data composed of 3 tertiary referral centers and national data. PATIENTS: Patients with primary colorectal lymphoma were identified within the Mayo Clinic (1990-2016) and the Surveillance, Epidemiology, and End Results database (1990-2014). MAIN OUTCOME MEASURES: Primary outcomes were overall and 5-year survival. RESULTS: For the institutional cohort (N = 82), 5-year survival was 79.9%. Five-year survival was higher for rectal (88.4%) than for colon tumors (77.2%; p = 0.004). On multivariable analysis, age <50 years was associated with higher overall survival (p = 0.04). Left-sided colon masses and aggressive histological subtypes were associated with worse survival (0.04 and 0.03). No effect of treatment modality on survival was noted. For the national cohort (N = 2942), 5-year survival was 58.4%. Five-year survival for rectal tumors was 61.0% and 57.8% for colon tumors. On multivariable analysis, factors associated with improved survival were age <70 y, (p < 0.0001), female sex (p = 0.005), right-sided masses (p = 0.02), and diagnoses after 2000 compared with 1990-1999 (p < 0.0001). Aggressive pathology (p < 0.0001) and stage III or stage IV presentation compared with stage I (p = 0.02 and p < 0.0001) were associated with worse survival. LIMITATIONS: The institutional cohort was limited by sample size to describe treatment effect on survival. A major limitation of the national cohort was the ability to describe treatment modalities other than surgery, including chemotherapy and/or no additional treatment. CONCLUSIONS: Poorer survival was noted in elderly patients and in those with aggressive pathology. An overall survival advantage was seen in women in the national cohort. Currently, optimal strategies should follow a patient-centered multidisciplinary approach. See Video Abstract at http://links.lww.com/DCR/A807. LINFOMA COLORECTAL PRIMARIO: EXPERIENCIA INSTITUCIONAL Y REVISIÓN DE UNA BASE DE DATOS NACIONAL: El linfoma colorectal primario es poco frecuente, representando del 0.2% al 0.6% de todos los cánceres colorectales. Debido a su baja incidencia y variedad histológica, no existen guías de tratamiento. OBJETIVO: El propósito fue reportar la experiencia en linfoma colorectal primario en una cohorte institucional y una nacional. DISEÑO:: Este fue un estudio de cohorte retrospectivo. ESCENARIO: El estudio se realizó con datos institucionales provenientes de 3 centros de referencia terciarios y datos nacionales. PACIENTES: Se identificaron pacientes con linfoma colorectal primario en la base de datos de la Clínica Mayo (1990-2016) y en la base de datos de vigilancia, epidemiología y resultados finales [Surveillance, Epidemiology, and End Results database (1990-2014)]. PRINCIPALES MEDIDAS DE RESULTADO: Los resultados primarios fueron la sobrevida general y a 5 años. RESULTADOS: Para la cohorte institucional (N = 82), la sobrevida a 5 años fue de 79.9%. La sobrevida a cinco años fue mayor en tumores rectales (88.4%) que en los de colon (77.2%; p = 0.004). En el análisis multivariable, la edad <50 años se asoció con una mayor sobrevida general (p = 0,04). Las masas de colon izquierdo y los subtipos histológicos agresivos se asociaron con una peor sobrevida (0.04 y 0.03). No se observó ningún efecto según la modalidad de tratamiento en la sobrevida. Para la cohorte nacional (N = 2942), la sobrevida a 5 años fue del 58.4%. La sobrevida a cinco años fue de 61.0% para los tumores rectales y 57.8% para los tumores de colon. En el análisis multivariable, los factores asociados con una mayor sobrevida fueron edad <70 años, (p <0.0001), sexo femenino (p = 0.005), masas derechas (p = 0.02) y los casos diagnósticados después del año 2000 comparados con los de 1990-1999 (p <0.0001). Histopatología agresiva (p <0.0001) y presentación en estadio III o estadio IV en comparación con estadio I (p = 0.02 y p <0.0001) se asociaron con una peor sobrevida. LIMITACIONES: La cohorte institucional estuvo limitada por el tamaño de la muestra para describir el efecto del tratamiento en la sobrevida. Una limitación mayor en la cohorte nacional fue la habilidad para describir modalidades de tratamiento distintas a la cirugía, incluyendo quimioterapia y/o ningún tratamiento adicional. CONCLUSIONES: Una menor sobrevida fue documentada en pacientes de edad avanzada y en aquellos con histopatología agresiva. Se observó ventaja en cuanto a sobrevida general en las mujeres de la cohorte nacional. Actualmente, las estrategias óptimas deben de seguir un abordaje multidisciplinario centrado en cada paciente. Vea el abstract en video en http://links.lww.com/DCR/A807.

Three-dimensional (3D) printing and its applications for aortic diseases.

Three-dimensional (3D) printing is a process which generates prototypes from virtual objects in computer-aided design (CAD) software. Since 3D printing enables the creation of customized objects, it is a rapidly expanding field in an age of personalized medicine. We discuss the use of 3D printing in surgical planning, training, and creation of devices for the treatment of aortic diseases. 3D printing can provide operators with a hands-on model to interact with complex anatomy, enable prototyping of devices for implantation based upon anatomy, or even provide pre-procedural simulation. Potential exists to expand upon current uses of 3D printing to create personalized implantable devices such as grafts. Future studies should aim to demonstrate the impact of 3D printing on outcomes to make this technology more accessible to patients with complex aortic diseases.

Degree of Left Renal Vein Compression Predicts Nutcracker Syndrome.

Nutcracker syndrome (NS) refers to symptomatic compression of the left renal vein (LRV) between the abdominal aorta and superior mesenteric artery with potential symptoms including hematuria, proteinuria, left flank pain, and renal venous hypertension. No consensus diagnostic criteria exist to guide endovascular treatment. We aimed to evaluate the specificity of LRV compression to NS symptoms through a retrospective study including 33 NS and 103 control patients. The size of the patent lumen at point of compression and normal portions of the LRV were measured for all patients. Multiple logistic regression analyses (MLR) assessing impact of compression, body mass index (BMI), age, and gender on the likelihood of each symptom with NS were obtained. NS patients presented most commonly with abdominal pain (72.7%), followed by hematuria (57.6%), proteinuria (39.4%), and left flank pain (30.3%). These symptoms were more commonly seen than in the control group at 10.6, 11.7, 6.8, and 1.9%, respectively. The degree of LRV compression for NS was 74.5% and 25.2% for controls (p < 0.0001). Higher compression led to more hematuria (p < 0.0013), abdominal pain (p < 0.006), and more proteinuria (p < 0.002). Furthermore, the average BMI of NS patients was 21.4 and 27.2 for controls (p < 0.001) and a low BMI led to more abdominal pain (p < 0.005). These results demonstrate a strong correlation between the degree of LRV compression on imaging in diagnosing NS.

Social Medicine: Twitter in Healthcare.

Social media enables the public sharing of information. With the recent emphasis on transparency and the open sharing of information between doctors and patients, the intersection of social media and healthcare is of particular interest. Twitter is currently the most popular form of social media used for healthcare communication; here, we examine the use of Twitter in medicine and specifically explore in what capacity using Twitter to share information on treatments and research has the potential to improve care. The sharing of information on Twitter can create a communicative and collaborative atmosphere for patients, physicians, and researchers and even improve quality of care. However, risks involved with using Twitter for healthcare discourse include high rates of misinformation, difficulties in verifying the credibility of sources, overwhelmingly high volumes of information available on Twitter, concerns about professionalism, and the opportunity cost of using physician time. Ultimately, the use of Twitter in healthcare can allow patients, healthcare professionals, and researchers to be more informed, but specific guidelines for appropriate use are necessary.

Minimally Invasive Limited Ligation Endoluminal-Assisted Revision (MILLER): A Review of the Available Literature and Brief Overview of Alternate Therapies in Dialysis Associated Steal Syndrome.

Dialysis associated steal syndrome (DASS) is a relatively rare but debilitating complication of arteriovenous fistulas. While mild symptoms can be observed, if severe symptoms are left untreated, DASS can result in ulcerations and limb threatening ischemia. High-flow with resultant heart failure is another documented complication following dialysis access procedures. Historically, open surgical procedures have been the mainstay of therapy for both DASS as well as high-flow. These procedures included ligation, open surgical banding, distal revascularization-interval ligation, revascularization using distal inflow, and proximal invasion of arterial inflow. While effective, open surgical procedures and general anesthesia are preferably avoided in this high-risk population. Minimally invasive limited ligation endoluminal-assisted revision (MILLER) offers both a precise as well as a minimally invasive approach to treating both dialysis associated steal syndrome as well as high-flow with resultant heart failure. MILLER is not ideal for all DASS patients, particularly those with low-flow fistulas. We aim to briefly describe the open surgical therapies as well as review both the technical aspects of the MILLER procedure and the available literature.

The Use of Transarterial Approaches in Peripheral Arteriovenous Malformations (AVMs).

Arteriovenous malformations (AVMs) are a subset of congenital vascular malformations (CVMs). They comprise abnormal connections between arterial and venous circulation; treatment approaches are dependent on the angioarchitecture of the AVM, specifically the number and arrangement of the feeder arteries and outflow veins. Various imaging modalities can be used to diagnose and plan treatment. Here we will review the use of transarterial approaches to treat AVMs.

Quadrilateral Space Syndrome: Diagnosis and Clinical Management.

Quadrilateral space syndrome (QSS) is a rare disorder characterized by axillary nerve and posterior humeral circumflex artery (PHCA) compression within the quadrilateral space. Impingement is most frequently due to trauma, fibrous bands, or hypertrophy of one of the muscular borders. Diagnosis can be complicated by the presence of concurrent traumatic injuries, particularly in athletes. Since many other conditions can mimic QSS, it is often a diagnosis of exclusion. Conservative treatment is often first trialed, including physical exercise modification, physical therapy, and therapeutic massage. In patients unrelieved by conservative measures, surgical decompression of the quadrilateral space may be indicated.

Multi-Detector Computed Tomography Imaging Techniques in Arterial Injuries.

Cross-sectional imaging has become a critical aspect in the evaluation of arterial injuries. In particular, angiography using computed tomography (CT) is the imaging of choice. A variety of techniques and options are available when evaluating for arterial injuries. Techniques involve contrast bolus, various phases of contrast enhancement, multiplanar reconstruction, volume rendering, and maximum intensity projection. After the images are rendered, a variety of features may be seen that diagnose the injury. This article provides a general overview of the techniques, important findings, and pitfalls in cross sectional imaging of arterial imaging, particularly in relation to computed tomography. In addition, the future directions of computed tomography, including a few techniques in the process of development, is also discussed.

Hemostasis and nanotechnology.

Hemorrhage accounts for significant morbidity and mortality. Various techniques have been employed to augment hemostasis from simple tourniquets to self-assembling nanoparticles. A growing understanding of the natural clotting cascade has allowed agents to become more targeted for potential use in different clinical scenarios. This review discusses current and developing hemostatic techniques, including matrix agents, external agents, biologically inspired agents, and synthetic and cell-derived nanoparticles.

Deep vein thrombosis: pathogenesis, diagnosis, and medical management.

Deep vein thrombosis (DVT) is a major preventable cause of morbidity and mortality worldwide. Venous thromboembolism (VTE), which includes DVT and pulmonary embolism (PE), affects an estimated 1 per 1,000 people and contributes to 60,000-100,000 deaths annually. Normal blood physiology hinges on a delicate balance between pro- and anti-coagulant factors. Virchow's Triad distills the multitude of risk factors for DVT into three basic elements favoring thrombus formation: venous stasis, vascular injury, and hypercoagulability. Clinical, biochemical, and radiological tests are used to increase the sensitivity and specificity for diagnosing DVT. Anticoagulation therapy is essential for the treatment of DVT. With few exceptions, the standard therapy for DVT has been vitamin K-antagonists (VKAs) such as warfarin with heparin or fractionated heparin bridging. More recently, a number of large-scale clinical trials have validated the use of direct oral anticoagulants (DOACs) in place of warfarin in select cases. In this review, we summarize the pathogenesis, diagnosis, and medical management of DVT, with particular emphasis on anticoagulation therapy and the role of DOACs in the current treatment algorithm.

Paget-Schroetter syndrome: treatment of venous thrombosis and outcomes.

Thoracic outlet syndrome (TOS) is a rare clinical entity with many etiologies. Venous thoracic outlet syndrome (VTOS), also called Paget-Schroetter syndrome (PSS), is a primary "effort" thrombosis. Here we will focus on the pathophysiology, anatomy, clinical presentation, treatments, and outcomes of VTOS. Treatment involves anticoagulation, catheter-directed thrombolysis, and surgical decompression. Early diagnosis and treatment can improve symptoms and quality of life.

Somatic growth trajectory in the fetus with hypoplastic left heart syndrome.

BACKGROUND: Fetal growth abnormalities in hypoplastic left heart syndrome (HLHS) have been documented primarily by birth measurements. Fetal growth trajectory has not been described. We hypothesized that fetal growth trajectory declines across late gestation in this population. METHODS: Infants with a prenatal diagnosis of HLHS and no history of prematurity or a genetic syndrome were identified. Fetal ultrasound measurements and birth anthropometrics were obtained from clinical records. z-Scores for estimated fetal weight (EFWz) and birth weight (BWTz) were compared. BWTz for three neonatal standards were compared. RESULTS: Paired fetal and neonatal data were identified in 33 cases of HLHS. Mean gestational age at ultrasound and birth were 27 and 38 wk, respectively. BWTz was lower than EFWz by a mean of 0.82 (SD: 0.72, P < 0.0001), with 64% of subjects demonstrating a decrease in z-score of >0.5. Umbilical artery (UA) Doppler found no evidence of significant placental insufficiency. Modest differences in BWTz were seen across BWT standards in this cohort. CONCLUSION: The majority of fetuses with HLHS demonstrate decreased growth velocity during later pregnancy, suggesting growth abnormalities manifest in utero. The potential relationship to future clinical outcomes warrants further study.

Microcephaly is associated with early adverse neurologic outcomes in hypoplastic left heart syndrome.

BACKGROUND: Hypoplastic left heart syndrome (HLHS) is associated with significant mortality and morbidity. Fetal head growth abnormalities have been identified in a subset of HLHS fetuses, but it is unclear whether specific patterns of maladaptive growth affect clinical outcomes. We hypothesized that poor fetal head growth is associated with an increased frequency of adverse clinical outcomes. METHODS: We retrospectively examined a cohort of HLHS patients from midgestation to 1 y of age. Fetal and birth anthropometric measurements were analyzed using the Olsen standard, and clinical outcomes were obtained. RESULTS: A total of 104 HLHS patients were identified over a 12-y period; fetal data were available in 38 cases. HLHS neonates demonstrated a high incidence of microcephaly (12%), small head size (27%), and poor head growth (32%). All-cause mortality was 31% at 30 d and 43% at 1 y. Neurologic outcomes were observed in 12% of patients and were significantly increased with microcephaly (43 vs. 4%; P = 0.02). The average length of hospital stay following stage I palliation was 33.4 ± 33 d, correcting for early death. CONCLUSION: In term nonsyndromic HLHS, fetal and neonatal microcephaly are associated with early adverse neurologic outcomes but not mortality.