Proficiency Development and Learning Curve in Robot-Assisted Spine Surgery Using the ExcelsiusGPS® System: Experience From a Single Institution.

STUDY DESIGN: Retrospective Cohort Study Objectives: Robot-assisted spine surgery (RASS) is a rapidly evolving technique with potential benefits for improving surgical outcomes. A number of studies on RASS learning curve have focused on early iterations of the Mazor robot. Limited research exists on the learning curve associated with using the Globus Medical ExcelsiusGPS® system. In this retrospective study, we aimed to evaluate the learning curve of RASS using the ExcelsiusGPS® system at a single institution. METHODS: A total of 95 patients (541 screws) who underwent RASS between 2021 and 2022 were included. Variables including operative time, robot registration time, screw placement time, fluoroscopy utilization, and complications were analyzed. Statistical analysis was performed using descriptive statistics and two-sample t-tests. RESULTS: The average operative time significantly decreased after the first 14 cases, indicating a learning curve. However, no significant improvement was observed in robot registration time. Notably, screw placement time significantly improved after approximately 13 cases. When controlling for the number of levels fused, the trends remained consistent. CONCLUSIONS: Our study confirmed the presence of a learning curve in RASS using the ExcelsiusGPS® system and demonstrated rapid proficiency development. Our findings highlight the relatively quick learning curve of 1 RASS system.

Fetal Pericardial Teratoma: Perinatal Management and Example of Preterm Cesarean Birth to Resection.

A very large fetal pericardial teratoma was diagnosed at 28 weeks' gestation, prompting urgent multidisciplinary expert consultations to weigh the risks and benefits of various prenatal invasive procedures and preterm delivery for postnatal surgical management. Ultimately, the infant was born by planned cesarean section and underwent immediate cardiopulmonary bypass and surgical resection.

Medical cannabis and its effect on oncological outcomes in patients with ovarian cancer treated with PARP inhibitors.

BACKGROUND: Poly (ADP-ribose) polymerase inhibitors (PARPi) play a pivotal role in ovarian cancer management. With medical cannabis emerging as a novel component of supportive care, this study investigated the impact of medical cannabis use on oncological outcomes in patients with ovarian cancer undergoing PARPi therapy. METHODS: The study included patients from a single institution database treated for ovarian cancer between January 2014 and January 2020 who received PARPi maintenance therapy in a first-line or recurrent disease setting after a confirmed response to platinum-based treatment. The study categorized patients as cannabis users and cannabis-naïve. Univariate and multivariate Cox regression analysis and the Kaplan-Meier method were used to assess the effects of medical cannabis use on the duration of PARPi therapy, progression-free survival, and overall survival. RESULTS: Among the eligible patients (n=93), most were cannabis-naïve (69%, n=64) while the rest used medical cannabis (31%, n=29). Medical cannabis use rates were comparable for patients receiving PARPi therapy post-primary treatment or for recurrence (42%, n=9, vs 27%, n=20; p=0.1). Both groups exhibited similar median duration for PARPi therapy (12.1 vs 9.5 months; p=0.89) and progression-free survival (20 vs 21 months; p=0.83). Kaplan-Meier analysis detected no differences in progression-free survival associated with cannabis use. Although cannabis users had an extended overall survival compared with the cannabis-naïve group (129.3 vs 99 months; p=0.03), cannabis use was insignificant for overall survival on multivariate analysis (p=0.10). Multivariate analysis showed stage IV at diagnosis (p=0.02) to be the sole factor associated with progression-free survival (p=0.02). CONCLUSION: Medical cannabis usage in patients receiving PARPi treatment showed no association with duration of PARPi therapy, progression-free survival, or overall survival.

Spectrum of Disease in Hospitalized Newborns with Congenital Micrognathia: A Cohort of 3,236 Infants at North American Tertiary-Care Intensive Care Units.

OBJECTIVE: To describe the spectrum of disease and burden of care in infants with congenital micrognathia from a multicenter cohort hospitalized at tertiary care centers. STUDY DESIGN: The Children's Hospitals Neonatal Database was queried from 2010 through 2020 for infants diagnosed with micrognathia. Demographics, presence of genetic syndromes, and cleft status were summarized. Outcomes included death, length of hospitalization, neonatal surgery, and feeding and respiratory support at discharge. RESULTS: Analysis included 3,236 infants with congenital micrognathia. Cleft palate was identified in 1266 (39.1%). A genetic syndrome associated with micrognathia was diagnosed during the neonatal hospitalization in 256 (7.9%). Median (IQR) length of hospitalization was 35 (16, 63) days. Death during the hospitalization (n = 228, 6.8%) was associated with absence of cleft palate (4.4%, P < .001) and maternal Black race (11.6%, P < .001). During the neonatal hospitalization, 1289 (39.7%) underwent surgery to correct airway obstruction and 1059 (32.7%) underwent gastrostomy tube placement. At the time of discharge, 1035 (40.3%) were exclusively feeding orally. There was significant variability between centers related to length of stay and presence of a feeding tube at discharge (P < .001 for both). CONCLUSIONS: Infants hospitalized with congenital micrognathia have a significant burden of disease, commonly receive surgical intervention, and most often require tube feedings at hospital discharge. We identified disparities based on race and among centers. Development of evidence-based guidelines could improve neonatal care.

Next-generation phenotyping: introducing phecodeX for enhanced discovery research in medical phenomics.

MOTIVATION: Phecodes are widely used and easily adapted phenotypes based on International Classification of Diseases codes. The current version of phecodes (v1.2) was designed primarily to study common/complex diseases diagnosed in adults; however, there are numerous limitations in the codes and their structure. RESULTS: Here, we present phecodeX, an expanded version of phecodes with a revised structure and 1,761 new codes. PhecodeX adds granularity to phenotypes in key disease domains that are under-represented in the current phecode structure-including infectious disease, pregnancy, congenital anomalies, and neonatology-and is a more robust representation of the medical phenome for global use in discovery research. AVAILABILITY AND IMPLEMENTATION: phecodeX is available at https://github.com/PheWAS/phecodeX.

Effects of EGFR driver mutations on pathologic regression in resectable locally advanced non-small cell lung cancer treated with neoadjuvant chemoradiation and completion surgery.

OBJECTIVE: We hypothesized that driver mutations in epidermal growth factor receptor (EGFR) are associated with decreased pathologic response to neoadjuvant chemoradiation (NA-ChRT) in locally advanced non-small cell lung cancer (LA-NSCLC). METHODS: Patients with Stage IIB-IIIA NSCLC treated with NA-ChRT, completion surgery, and underwent molecular profile testing were identified in a lung cancer database. Pathologic response was quantified using: (i) major pathologic response (MPR), (ii) complete pathologic response (pCR), and (iii) mean residual viable tumor cells (MRTC). Two groups were formed based on the presence or absence of driver mutations. Clinical and pathological correlations between the groups were studied. RESULTS: Forty-seven patients underwent tumor molecular profile testing, NA-ChRT, and completion surgery. Compared to the no-driver mutation group, the driver mutation group had lower MPR (23% vs 71%, p = 0.003), pCR (0% vs 26%, p = 0.02), and higher MRTC (43.4% vs 15.8%, p = 0.009). Univariate analysis showed an increased MPR rate for smokers, squamous cell histology, ChRT-surgery interval >65 days, and no-driver mutations. Multivariate analysis showed that only no-driver mutations (OR 0.39, p = 0.02) remained significant for MPR. PD-L1 status did not affect MPR. At 2 years, the driver mutation group had lower rates of local control (Hazard ration [HR] 0.67, p = 0.17) and disease-free survival (HR 0.5, p = 0.001). Overall survival was similar for both groups (HR = 1.04, p = 0.86). CONCLUSION: Following 60 Gray NA-ChRT, tumors with a driver mutation had lower MPR and pCR rates than tumors without a driver mutation. PD-L1 was not associated with tumor regression. ADVANCES IN KNOWLEDGE: Patients with resectable LA-NSCLC and an EGFR driver mutation treated with neoadjuvant-ChRT and completion surgery have reduced pathologic regression, lower local control rates, and shorter disease-free survival than patients without a driver mutation. Evaluation of molecular testing should be introduced in LA-NSCLC intended for prognostication and treatment decisions.

The impact of HIV and ART exposure during pregnancy on fetal growth: a prospective study in a South African cohort.

BACKGROUND: In utero exposure to human immunodeficiency virus (HIV) and antiretroviral (ART) is associated with adverse birth outcomes, which are often attributed to alterations in placental morphology. This study used structural equation models (SEMs) to examine the impact of HIV and ART exposure on fetal growth outcomes and whether these associations are mediated by placental morphology in urban-dwelling Black South African women. METHODS: This prospective cohort study included pregnant women living with HIV (WLWH, n = 122) and not living with HIV (WNLWH, n = 250) that underwent repeated ultrasonography during pregnancy, and at delivery, to determine fetal growth parameters in Soweto, South Africa. The size and the velocity of fetal growth measures (i.e., head and abdominal circumference, biparietal diameter, and femur length) were calculated using the Superimposition by Translation and Rotation. Placenta digital photographs taken at delivery were used to estimate morphometric parameters and trimmed placental weight was measured. All WLWH were receiving ART for the prevention of vertical transmission of HIV. RESULTS: A trend towards a lower placental weight and significantly shorter umbilical cord length was reported in WLWH compared to their counterparts. After sex stratification, umbilical cord length was significantly shorter in males born to WLWH than in male fetuses born to WNLWH (27.3 (21.6-32.8) vs. 31.4 (25.0-37.0) cm, p = 0.015). In contrast, female fetuses born to WLWH had lower placental weight, birth weight (2.9 (2.3-3.1) vs. 3.0 (2.7-3.2) kg), and head circumference (33 (32-34) vs. 34 (33-35) cm) than their counterparts (all p ≤ 0.05). The SEM models showed an inverse association between HIV and head circumference size and velocity in female fetuses. In contrast, HIV and ART exposure was positively associated with femur length growth (both size and velocity) and abdominal circumference velocity in male fetuses. None of these associations appeared to be mediated via placental morphology. CONCLUSION: Our findings suggest that HIV and ART exposure directly affects head circumference growth in females and abdominal circumference velocity in male fetuses; but may improve femur length growth in male fetuses only.

Surgical outcome and treatment trends in 1289 infants with micrognathia: a multicenter cohort.

BACKGROUND: Studies of infants with micrognathia, especially Robin Sequence (RS), are limited by its rarity and both phenotypic and diagnostic variability. Most knowledge of this condition is sourced from small, single-institution samples. METHODS: This is a cross-sectional study including infants with micrognathia admitted to 38 Children's Hospital Neonatal Consortium centers from 2010-2020. Predictor variables included demographic data, birth characteristics, cleft and syndrome status. Outcome variables included length of stay (LOS), death, feeding or respiratory support, and secondary airway operations. RESULTS: 1289 infants with micrognathia had a surgery to correct upper airway obstruction. Mean age and weight at operation were 34.8±1.8 weeks and 3515.4±42 grams, respectively. A syndromic diagnosis was made in 150 (11.6%) patients, with Stickler (5.4%) and Treacher Collins Syndromes (2.2%) most common. Operations included: mandibular distraction osteogenesis (MDO), 66.3%; tracheostomy, 25.4%; and tongue-lip adhesion (TLA), 8.3%. Tracheostomy patients had a lower birth weight, head circumference, gestational age, and APGAR scores. MDO patients were less likely to need a second airway operation compared to TLA patients (3.5%vs17.8%,p<0.001). The proportion of infants feeding exclusively orally at hospital discharge differed significantly, from most to least: MDO, TLA, tracheostomy. Hospital LOS was not statistically different for patients that had MDO and TLA, but was longer for those with primary tracheostomy. Mortality was low for all operations (0.5%). CONCLUSION: In this 1289 surgical patient cohort, MDO was associated with shorter hospital stay, improved oral feeding, and lower rates of secondary airway operations. Prospective multi-center studies are necessary to support these conclusions.

Analysis of placental pathology after COVID-19 by timing and severity of infection.

BACKGROUND: COVID-19 during pregnancy can have serious effects on pregnancy outcomes. The placenta acts as an infection barrier to the fetus and may mediate adverse outcomes. Increased frequency of maternal vascular malperfusion has been detected in the placentas of patients with COVID-19 compared with controls, but little is known about how the timing and severity of infection affect placental pathology. OBJECTIVE: This study aimed to examine the effects of SARS-CoV-2 infection on placental pathology, specifically whether the timing and severity of COVID-19 affect pathologic findings and associations with perinatal outcomes. STUDY DESIGN: This was a descriptive retrospective cohort study of pregnant people diagnosed with COVID-19 who delivered between April 2020 and September 2021 at 3 university hospitals. Demographic, placental, delivery, and neonatal outcomes were collected through medical record review. The timing of SARS-CoV-2 infection was noted, and the severity of COVID-19 was categorized on the basis of the National Institutes of Health guidelines. The placentas of all patients with positive nasopharyngeal reverse transcription-polymerase chain reaction COVID-19 testing were sent for gross and microscopic histopathologic examinations at the time of delivery. Nonblinded pathologists categorized histopathologic lesions according to the Amsterdam criteria. Univariate linear regression and chi-square analyses were used to assess how the timing and severity of SARS-CoV-2 infection affected placental pathologic findings. RESULTS: This study included 131 pregnant patients and 138 placentas, with most patients delivered at the University of California, Los Angeles (n=65), followed by the University of California, San Francisco (n=38) and Zuckerberg San Francisco General Hospital (n=28). Most patients were diagnosed with COVID-19 in the third trimester of pregnancy (69%), and most infections were mild (60%). There was no specific placental pathologic feature based on the timing or severity of COVID-19. There was a higher frequency of placental features associated with response to infection in the placentas from infections before 20 weeks of gestation than that from infections after 20 weeks of gestation (P=.001). There was no difference in maternal vascular malperfusion by the timing of infection; however, features of severe maternal vascular malperfusion were only found in the placentas of patients with SARS-CoV-2 infection in the second and third trimesters of pregnancy, not in the placentas of patients with COVID-19 in the first trimester of pregnancy. CONCLUSION: Placentas from patients with COVID-19 showed no specific pathologic feature, regardless of the timing or severity of the disease. There was a higher proportion of placentas from patients with COVID-19-positive tests in earlier gestations with evidence of placental infection-associated features. Future studies should focus on understanding how these placental features in SARS-CoV-2 infections go on to affect pregnancy outcomes.

Interactions between maternal health and placental morphology on neonate body composition.

Background: We aimed to examine maternal metabolic correlates of neonate body composition, and the potential mediating effect of the placenta. Methods: Data were collected throughout pregnancy and at delivery. An oral glucose tolerance test (OGTT) was conducted in order to diagnose or rule out gestational diabetes mellitus (GDM). Maternal weight and blood pressure were taken and hypertension and gestational weight gain (GWG) were defined. Gestational age, birth weight (BW) and weight to length ration (WLR) were recorded. Photographs were taken of the placenta, and the widths and lengths were measured digitally. Body composition was analysed via air displacement plethysmography or dual-energy x-ray absorptiometry. Mediation models were conducted to determine the mediation effect of the placental variables on the relationships between maternal health variables and neonate outcomes. Next, interaction terms were added to models to determine how maternal and placental variables interacted in their effect on neonate outcomes. Results: A total of n = 280 women were included in the analysis. Majority were overweight or obese. Fourteen percent of women developed GDM during pregnancy, 5% had hypertension during pregnancy, 32% were HIV positive, and 32% had anemia. For the birth weight outcome, coefficients of BMI were attenuated by the addition of placental variables (Model 1 ß=18.66 vs Model 2 ß=16.40). Similar patterns were evident for GWG and hypertension, and for the WLR outcome. In all cases the addition of the placental variables attenuated associations between maternal exposures and neonatal outcomes, yet the level of significance did not change. Inclusion of interaction terms reversed the direction of the relationships between hypertension and BW and WLR, and between GWG and WLR. Conclusion: The placenta buffers some harmful effects of obesity, GWG, and hypertension on neonate size, and placental efficiency interacted with most maternal risk factors to either counteract, or attenuate relationships with neonate size at birth. However the placenta was unable to completely counteract the negative effect of excess nutrient supply on in utero growth.

Outcomes associated with treatment to all sites of disease in patients with stage IVB cancer of the cervix.

OBJECTIVE: The use of chemoradiation in patients with stage IVB cancer of the cervix was evaluated to determine if definitive treatment offers benefit. METHODS: A database of 546 patients with cancer of the cervix treated between January 2005 and May 2021 at a tertiary academic medical center was reviewed retrospectively to identify patients with stage IVB disease. Log rank test, regression analysis, and the Kaplan-Meier method were used to identify and compare variables and estimate progression free survival and overall survival. RESULTS: Thirty-three patients with stage IVB cervical cancer were identified. Median age was 53 years (range 28-78). Pathology subtypes were squamous cell (n=22, 67%), adenocarcinoma (n=8, 24%), and clear cell (n=3, 9%). Metastases were classified as lymphatic (n=14, 42%) or hematogenous (n=19, 58%). Following treatment to all sites with chemoradiotherapy and selected use of surgery (n=23), six patients (26%, lymphatic n=4, hematogenous n=2) remained disease free for a median duration of 4 years (range 3-17 years). Recurrences in the remaining patients were distant (n=13) or local (n=4). All patients in the chemotherapy group (n=10, 100%) progressed. Kaplan-Meier analysis showed that median progression free survival was longer for patients treated at all disease sites than for patients treated with chemotherapy alone (19 vs 11 months, p=0.01). However, this was not the case for overall survival (49 vs 33 months, p=0.15). Patients with metastases limited to lymph nodes also had longer median progression free survival (22 vs 11 months, p=0.04) but not overall survival (p=0.68). CONCLUSIONS: Patients with stage IVB cancer of the cervix may benefit from treatment to all sites of disease, if feasible and safe, as demonstrated by improved progression free survival.

Vascular malperfusion and abruption are prevalent in placentas from pregnancies with congenital heart disease and not associated with cardiovascular risk.

Congenital heart disease (CHD) in pregnancy is associated with an increased risk of adverse maternal, obstetric, and neonatal outcomes, plausibly through mechanisms involving abnormal placental development and function. This retrospective study aims to elucidate how maternal CHD influences placental health. Demographic and clinical information were collected via electronic medical record review, and placentas underwent histopathological evaluation. Fifty-three singleton pregnancies were included: 35 participants (66%) were classified as lower cardiovascular risk (modified World Health Organization Classification (mWHO) I, II, II-III), and 18 (34%) were classified as higher cardiovascular risk (mWHO III, IV). 12 participants (23%) had a fetus with small for gestational age (SGA). Maternal vascular malperfusion (53%) and placental abruption (11.6%) were common in this cohort, with prevalence above baseline risk. Participants at higher cardiovascular risk had higher rates of SGA (p = 0.04), subchorionic hematomas (p = 0.01) and birth weight:placental weight < 10th percentile (p = 0.04), but did not differ in rates of maternal vascular malperfusion (p = 0.15) compared to those at lower cardiovascular risk. In pregnancies with maternal CHD, SGA and histologic evidence of maternal vascular malperfusion and placental abruption were common, though patients at higher cardiovascular risk did not show evidence of worsened placental health compared to those at lower risk.

Association of Intraoperative Frozen Section Controls With Improved Margin Assessment During Transoral Robotic Surgery for Human Papillomavirus-Positive Oropharyngeal Squamous Cell Carcinoma.

Importance: Intraoperative margin assessment is an important technique for ensuring complete tumor resection in malignant cancers. However, in patients undergoing transoral robotic surgery (TORS) for oropharyngeal carcinomas, tissue artifact may provide pathologic uncertainty. Objective: To assess the benefit of providing frozen section control samples ("positive tumor biopsies") for use during intraoperative margin assessment for patients undergoing TORS for human papillomavirus (HPV)-16-positive oropharyngeal squamous cell carcinoma (OPSCC). Design, Setting, and Participants: In this cohort study, patients receiving curative-intent TORS for biopsy-proven HPV-16-positive OPSCC performed by a single attending surgeon (A.H.M.) at Ronald Reagan UCLA Medical Center from 2017 to 2021 were included in a retrospective data analysis. Exclusion criteria included HPV-negative status, participation in clinical trials, and tumors of unknown primary origin. Main Outcomes and Measures: Survival outcomes investigated included overall and disease-free survival. Adverse pathologic outcomes measured included occurrence of nondiagnostic margins and margin reversal from frozen to fixed pathology. Results: Of the 170 patients included (mean [SD] age, 61.8 [9.9] years; 140 [82%] male), 50% of patients (n = 85) received a frozen section control. Use of a frozen section control was associated with statistically significantly improved sensitivity of intraoperative margin assessment, from 82.8% to 88.9% (difference, 6.1%; 95% CI, 3.9%-8.3%). Eleven percent (n = 18) of all tumors evaluated exhibited at least 1 nondiagnostic intraoperative margin, and 11% (n = 18) experienced margin reversal from frozen to fixed pathology. In patients with nondiagnostic margins, use of frozen section controls was associated with statistically significantly reduced time spent in the operating room (Cohen d, 1.14; 95% CI, 0.12-2.14). Conclusions and Relevance: In this cohort study, frozen intraoperative margins assessed during TORS resections of HPV-16-positive OPSCC were diagnostically challenging. Adverse pathologic outcomes, such as margin status reversal from positive on frozen pathology to negative on formal analysis, were common. Providing intraoperative frozen section control biopsies may offer clarity in cases with nondiagnostic margins, reducing the need for additional sampling and time spent in the operating room.

Relationships between adiposity distribution and metabolic health in preconception women in South Africa.

Objective: Adipose tissue is a central regulator of metabolic health and a contributor to systemic inflammation. Patterns of adiposity deposition are important to understand for optimizing health. This study aimed to asses relationships between adiposity deposition and metabolic and inflammatory biomarkers in South African women prior to conception. Methods: Non-pregnant, healthy women (n = 298) were recruited for this cross-sectional study via home visits. Body composition was measured by Dual X-ray Absorptiometry. Inflammation markers C-reactive protein (CRP), alpha1-acid glycoprotein (AGP), hemoglobin A1c (HbA1c), and blood pressure were scored according to risk. A summative metabolic health risk score was created for women with obesity. Generalized regression models assessed relationships between adiposity deposition and outcomes with adjustment for potential confounders. Results: Obesity was present in 22% of women (mean age = 20.93 years). Fat mass index was associated with inflammation and metabolic health risk (ß = 0.58; p < 0.01). Visceral fat, trunk:limb ratio, android:gynoid ratio, body mass index, weight, and waist circumference were positively associated with CRP, AGP, and metabolic health risk (p < 0.01). Weight was associated with Hba1c (ß < 0.01; p < 0.05). Participants with obesity and low metabolic health risk had lower fat mass index and visceral fat than participants with obesity and higher metabolic health risk. Conclusions: Black South African women accumulated excess adipose tissue in abdominal regions. While fat mass and body mass were associated with inflammation and metabolic health risk, women with obesity and with lower fat mass index and lower visceral adipose tissue were metabolically protected. Identification of women at risk for metabolic disease preconception could help ensure future healthy pregnancies and prevent transference of risk to offspring.

Intrathecal Fentanyl With a Myofascial Plane Block in Open Lumbar Surgeries: A Case Series.

BACKGROUND: Acute postoperative pain control after lumbar surgery is imperative to minimizing long-term narcotic use and associated adverse sequela. The safety of intrathecal morphine for postoperative pain management in spine surgery has been investigated; however, to date, no studies have investigated the safety of intrathecal fentanyl with a myofascial plane (MP) block in lumbar procedures. OBJECTIVE: To assess the safety profile of intrathecal fentanyl with a MP block administered during lumbar surgery and the subsequent utilization of postoperative intravenous opioids. METHODS: An intraoperative intrathecal injection of fentanyl and a MP block was administered in 40 patients undergoing open lumbar reconstructive surgery. The procedure performed was an open decompression with lumbar total joint reconstruction at 1 to 3 lumbar levels. Postoperative complications including urinary retention, respiratory depression, and need for IV opioid use were recorded. RESULTS: Postoperatively, none of the study patients required IV opioid medication for supplemental pain control. Thirty-six patients (85%) were discharged same day or before 23 hours postoperatively. No intrathecal fentanyl-related perioperative complications were noted. None of the 40 listed patients experienced urinary retention or delayed respiratory depression. One patient (2%) experienced orthostatic hypotension at postoperative day 1, which resolved on discontinuation of oral oxycodone. CONCLUSION: Intrathecal fentanyl and MP block may be a safe option for perioperative pain control and may reduce the need for supplemental intravenous opioids without increased risk of respiratory depression, urinary retention, or other side effects. Further studies are necessary to compare the efficacy of intrathecal fentanyl with other analgesia techniques.

Chemoradiation followed by adjuvant durvalumab in stage III non-small cell lung cancer: Real-world comparison of treatment outcomes to historical controls treated with chemoradiation alone.

OBJECTIVE: Compare outcomes in patients with stage III non-small cell lung cancer (NSCLC) treated with chemoradiation and adjuvant durvalumab to historical controls treated with chemoradiation alone. METHODS: The records of patients with stage III NSCLC treated with definitive chemoradiation ± adjuvant durvalumab were reviewed retrospectively. Primary endpoints were progression free survival (PFS), overall survival (OS), and adverse events (AE). RESULTS: Between September 2009 and September 2020, 215 patients were treated with concurrent chemoradiation (n = 144) or concurrent chemoradiation followed by adjuvant durvalumab (n = 71). Compared to historical controls, durvalumab use was associated with improved PFS: median (27 months vs. 10 months, p < 0.0001), 1-year (83.1% vs. 43.8, p < 0.0001); and improved OS; median (not reached vs. 24 months, p < 0.0001), 1-year (85.9% vs. 81.9%, p < 0.0001). Multivariate analysis showed adjuvant durvalumab was associated with increased OS (p = 0.005) and PFS (p = 0.001). Within the durvalumab group, only clinical stage IIIA versus IIIB/C was associated with improved OS (p = 0.049), but not PFS. There was no association between PFS or OS and Eastern Cooperative Oncology Group (ECOG) score, prior history of immune disease, programmed death-ligand 1 (PD-L1) receptor status, delay in starting durvalumab beyond 42 days, or development of an AE. During durvalumab treatment, 63 AE were reported in 52 patients with treatment discontinuation in 11. Pneumonitis was the most common AE reported (n = 35, 49%). Most AE were grade 1-2 (n = 57). Grade 3-4 AE were uncommon (n = 6) and none were grade 5. CONCLUSION: Treatment with adjuvant durvalumab following chemoradiation was associated with improved PFS and OS compared to chemoradiation alone.

In Scheuermann's kyphosis, a proximal UIV and postop kyphosis value close to patients' PI decreases the risk of PJK.

PURPOSE: Prevalence of proximal junctional kyphosis (PJK) in Scheuermann's kyphosis (SK) varies between 24 and 40%. Multiple factors have been implicated, including kyphosis overcorrection, failure to include proximal end vertebra, and implant choice. This study aimed to determine the goal correction parameters based upon patients' pelvic incidence, and UIV to decrease PJK in Scheuermann's kyphosis. METHODS: X-ray and chart review of SK patients operated with all pedicle screw (PS), hybrid fixation (HF), and anterior/posterior fusions with hybrid fixation (AP). T1/T2 were grouped together as proximal fusion groups compared to T3 and distal groups. RESULTS: 96 total patients: PS (n = 41), HF (n = 24), and AP (n = 31). Overall, at early postop 12 (12.5%) patients had PJK. At final follow-up, 33 (34.4%) had PJK. There was no significant difference between groups at early postop (p = 0.86) or final follow-up (p = 0.67). When correcting kyphosis-PI to > - 10.0° and UIV was chosen to be T1 or T2, PJK developed in 6.1% of patients at final follow-up; when fusing to T1/T2 but with kyphosis-PI < - 10.0°, 38.9% of patients developed PJK. With kyphosis-PI > - 10.0° and UIV at T3 or below, 37.0% of patients developed PJK at final follow-up. When fusing to T3 or below but failing to correct kyphosis-PI to > - 10.0°, 77.8% of patients developed PJK. CONCLUSION: Selecting proximal UIV and avoiding kyphosis-PI mismatch can significantly decrease the prevalence of PJK rather than surgical technique or implant choice. Surgeons treating SK should, therefore, aim to correct kyphosis closer to the patient's pelvic incidence and choose T2/T1 as UIV.

Initial estimates of continuous positive airway pressure (CPAP) on heart volume, position and motion in patients receiving chest radiation.

To evaluate effects of Continuous Positive Airway Pressure (CPAP) on cardiac position, volume, and motion in a cohort of patients receiving thoracic radiation therapy (RT). Patients underwent 3-dimensional (3D) and 4D-computerized tomography (CT) imaging with free-breathing (FB) and CPAP for RT planning. All scans were co-registered on the treatment planning system for contouring, identification of the center of heart volume and comparative measurements of cardiac displacement, volume and motion. Heart volume (HV) was created from 3D-CT contours. Range of heart motion was estimated by creating an internal heart volume (IHV) from 4D-CT contours. Magnitude of cardiac motion (cardiac excursion) was recorded as the difference in volume between IHV and HV. Wilcoxon signed rank test and Spearmen's rank correlation coefficient were used to assess differences between variables and correlations between lung volume and heart parameters. Results from 9 patient data sets were available for this report. Compared to FB, CPAP use was associated with caudal displacement of the HV (1 cm, p < 0.008) and IHV (1.1 cm, p < 0.008). CPAP use decreased HV 6% (p < 0.008) and IHV 13% (p < 0.008). Cardiac excursion was 49% (p < 0.01) less with CPAP than with FB. CPAP use increased mean lung volume by 30% (p < 0.008) which correlated with caudal displacement of the HV (r = 0.83, p < 0.008) and IHV (r = 0.98, p < 0.001). The use of CPAP reduced cardiac motion and volume although the reduction in volume was minimal. The increase in lung volume correlated with caudal displacement of the heart. These results suggest the mechanism for achieving dosimetric benefit was obtained by cardiac displacement and decreased lung and heart motion rather than reduction of HV. Further evaluation of CPAP as a novel technique to reduce heart exposure when offering RT is warranted.

Genomic answers for children: Dynamic analyses of >1000 pediatric rare disease genomes.

PURPOSE: This study aimed to provide comprehensive diagnostic and candidate analyses in a pediatric rare disease cohort through the Genomic Answers for Kids program. METHODS: Extensive analyses of 960 families with suspected genetic disorders included short-read exome sequencing and short-read genome sequencing (srGS); PacBio HiFi long-read genome sequencing (HiFi-GS); variant calling for single nucleotide variants (SNV), structural variant (SV), and repeat variants; and machine-learning variant prioritization. Structured phenotypes, prioritized variants, and pedigrees were stored in PhenoTips database, with data sharing through controlled access the database of Genotypes and Phenotypes. RESULTS: Diagnostic rates ranged from 11% in patients with prior negative genetic testing to 34.5% in naive patients. Incorporating SVs from genome sequencing added up to 13% of new diagnoses in previously unsolved cases. HiFi-GS yielded increased discovery rate with >4-fold more rare coding SVs compared with srGS. Variants and genes of unknown significance remain the most common finding (58% of nondiagnostic cases). CONCLUSION: Computational prioritization is efficient for diagnostic SNVs. Thorough identification of non-SNVs remains challenging and is partly mitigated using HiFi-GS sequencing. Importantly, community research is supported by sharing real-time data to accelerate gene validation and by providing HiFi variant (SNV/SV) resources from >1000 human alleles to facilitate implementation of new sequencing platforms for rare disease diagnoses.

Impact of Discharge to Rehabilitation on Postdischarge Morbidity Following Multilevel Posterior Lumbar Fusion.

STUDY DESIGN: This was a retrospective cohort study. OBJECTIVE: The objective of this study was to compare 30-day postdischarge morbidity for 3-or-more level (multilevel) posterior lumbar fusion in patients who were discharged to home versus rehabilitation. SUMMARY OF BACKGROUND DATA: Spine surgery has been increasingly performed in the elderly population, with many of these patients being discharged to rehabilitation and skilled nursing facilities. However, research evaluating the safety of nonhome discharge following spine surgery is limited. MATERIALS AND METHODS: Patients who underwent multilevel posterior lumbar fusion from 2005 to 2018 were identified using the National Surgical Quality Improvement Program (NSQIP) database. Regression was utilized to compare primary outcomes between discharge disposition and to evaluate for predictors thereof. RESULTS: We identified 5276 patients. Unadjusted analysis revealed that patients who were discharged to rehabilitation had greater postdischarge morbidity (5.6% vs. 2.6%). After adjusting for baseline differences, discharge to rehabilitation no longer predicted postdischarge morbidity [odds ratio (OR)=1.409, confidence interval: 0.918-2.161, P=0.117]. Multivariate analysis also revealed that age (P=0.026, OR=1.023), disseminated cancer (P=0.037, OR=6.699), and readmission (P<0.001, OR=28.889) independently predicted postdischarge morbidity. CONCLUSIONS: Thirty days morbidity was statistically similar between patients who were discharged to home and rehabilitation. With appropriate patient selection, discharge to rehabilitation can potentially minimize 30-day postdischarge morbidity for more medically frail patients undergoing multilevel posterior lumbar fusion. These results are particularly important given an aging population, with a great portion of elderly patients who may benefit from postacute care facility discharge following spine surgery.