Improved survival with immunotherapy for microsatellite unstable colorectal cancer with peritoneal metastases.

BACKGROUND: KEYNOTE-177 demonstrated that immunotherapy was superior to chemotherapy for microsatellite-instability-high (MSI-high) metastatic colorectal cancer. Colorectal cancer with peritoneal metastases (CRPM) has a poorer prognosis than other metastatic sites, with an unclear role of immunotherapy. We evaluated trends in immunotherapy use and overall survival (OS). METHODS: Patients with CRPM and MSI testing were identified in the National Cancer Database (2016-2020). We evaluated immunotherapy use by year and associated patient/hospital factors. OS was compared for immunotherapy versus chemotherapy, cytoreductive surgery (CRS), and immunotherapy plus CRS. RESULTS: Among 15 322 CRPM patients, 7072 (46.2%) patients had documented MSI testing, with 819 (11.6%) MSI-high. Ninety-eight MSI-high patients received immunotherapy alone (12.3%), increasing from 0% in 2016 to 19.1% in 2020 (p < 0.01). On multivariable analysis, only higher comorbidity was associated with immunotherapy (OR: 2.83 [1.22-6.52]). Two-year OS with immunotherapy versus chemotherapy was 64.2% versus 54.1% (p < 0.05). In patients receiving CRS plus systemic therapy (N = 96), 2-year OS was 68.4%. Among patients who underwent immunotherapy and CRS versus immunotherapy alone, 2-year OS was 80.0% versus 60.0% (p = 0.14). CONCLUSIONS: Immunotherapy was associated with significantly better survival compared to chemotherapy in MSI-high CRPM. Two-year OS with systemic + CRS was 68.4%. Despite its role in guiding treatment, MSI testing remains low for these patients.

Adoption of cytoreductive surgery in the management of peritoneal malignancies-Global trends.

Cytoreductive surgery (CRS) has now been accepted as an integral component in the management of gastrointestinal and gynecological cancers with peritoneal metastases. Since the adoption of CRS is influenced by access to advanced medical facilities, trained multidisciplinary teams, and funding, there is wide variability in incorporation of CRS into routine clinical practice between high- versus low- and middle-income countries. This review highlights the global trends in the adoption of CRS for peritoneal malignancies with a specific focus on the establishment of CRS programs and barriers to incorporate CRS into routine clinical care in low- and middle-income countries.

Elastofibroma Dorsi: Case Series of a Rare Chest Wall Pseudotumor.

BACKGROUND: Elastofibroma dorsi (EFD) is a pseudotumor of the thoracic wall that can be difficult to diagnose due to its rarity. Prompt recognition can limit unnecessary workup and expedite treatment. This study retrospectively analyzed patients with a diagnosis of EFD, discussing clinical presentations and surgical outcomes. METHODS: This is an IRB-approved single-center retrospective study of all patients with a diagnosis of elastofibroma at our institution between 2000 and 2022. RESULTS: Ten patients were identified to have a pathologic diagnosis of EFD since 2000, with half presenting in the last 5 years. Our cohort had an average age of 56.8 years and was 50% female. The average age of male subjects was younger than females, 49.6-64.0 years, respectively (p = 0.10). Eighty percent (8/10) of patients had unilateral EFDs and symptoms lasted 27.1 months on average prior to diagnosis. Surgical resection was performed on 66.67% (8/12) of masses, with 87.5% (7/8) of patients who underwent surgery reporting complete resolution of their symptoms and none reporting recurrence. CONCLUSIONS: Although EFD is a rare pseudotumor, its incidence may be increasing. As such, surgeons should be aware of the typical clinical presentation; specifically, a slow growing, predominantly unilateral, painful, subscapular mass with an inhomogeneous pattern on imaging. Originally thought to predominantly affect elderly women, our study shows that younger men may be at risk as well. If patients present with EFD, complete surgical resection should be performed to achieve favorable outcomes and resolution of symptoms.

Endoscopic third ventriculostomy inpatient failure rates compared with shunting in post-hemorrhagic hydrocephalus of prematurity.

PURPOSE: Endoscopic third ventriculostomy (ETV) has gained traction as a method for treating post-hemorrhagic hydrocephalus of prematurity (PHHP) in an effort to obviate lifelong shunt dependence in neonates. However, data remains limited regarding inpatient failures. METHODS: A retrospective analysis of the NIS between 1998 and 2014 was performed. Discharges with age < 1 year and ICD-9-CM codes indicating intraventricular hemorrhage of prematurity (772.1x) and ETV/shunt (02.22 and 02.3x) were included. Patients with ICD-9-CM codes for ventricular drain/reservoir (02.21) were excluded to prevent confounding. Time trend series plots were created. Yearly trends were quantified using logarithmic regression analysis. Kaplan-Meier curves were utilized to analyze time to treatment failure. Time to failure for each treatment was compared using log-rank. RESULTS: A total of 11,017 discharges were identified. ETV was more likely to be utilized at < 29 weeks gestational age (p = 0.0039) and birth weight < 1000 g (p = 0.0039). Shunts were less likely to fail in older and heavier newborns (OR 0.836 p = 0.00456, OR 0.828 p = 0.0001, respectively). Those initially shunted had lower failure rates compared with ETV (OR 0.44, p < 0.0001) but time to failure was longer with ETV (p = 0.04562). 79.5% of ETVs that failed were shunted after the first failure. Shunts were much less likely to undergo ETV if they failed (OR 0.21, p < 0.0001). Higher grade IVH was predictive of shunt failure but not ETV (OR 2.36, p = 0.0129). CONCLUSIONS: Although ETV can be effective in PHHP, it has a much higher initial failure rate than shunting and should thus be chosen based on a multifactorial approach.

Evaluating predictors of mortality in octogenarians undergoing urgent or emergent trauma laparotomy.

PURPOSE: This study aimed to identify associated risk factors for mortality in octogenarian trauma patients undergoing urgent or emergent laparotomy (UEL). METHODS: Trauma patients ages 80-89 years-old undergoing UEL within 6-hours of arrival were included. A multivariable logistic regression analysis was performed to determine associated risk of mortality. RESULTS: From 701 octogenarians undergoing UEL, 324 (46.2%) died. Compared to survivors, UEL octogenarians who died had higher rates of cirrhosis (3.5% vs. 1.1%, p = 0.028), injuries to the brain (17.3% vs. 5.6%, p < 0.001), heart (8.6% vs. 1.6%, p < 0.001), and lung (57.4% vs. 23.9%, p < 0.001) and lower rates of functional independence (6.4% vs. 12.6%, p = 0.007). The strongest independent associated patient-related risk factor for death was cirrhosis (OR 8.28, CI 2.25-30.46, p = 0.001). However, undergoing concurrent thoracotomy increased risk of death significantly (OR 16.59, CI 2.07-132.76, p = 0.008). Functional independence was not associated with mortality (p > 0.05). CONCLUSION: This national analysis emphasizes the need to identify and manage pre-existing conditions like cirrhosis and not determine futility based on pre-trauma functional status alone. Concurrent thoracotomy for hemorrhage control increases risk of death over 16-fold.

Regional Therapy Approaches for Gastric Cancer with Limited Peritoneal Disease.

PURPOSE: Despite advances in systemic therapy, outcomes of patients with gastric cancer (GC) peritoneal carcinomatosis (PC) remain poor, in part because of poor penetrance of systemic therapy into peritoneal metastasis due to the plasma-peritoneal barrier and anarchic intra-tumoral circulation. Hence, regional treatment approach with administration of chemotherapy directly into the peritoneal cavity (intraperitoneal, IP) under various conditions, combined with or without cytoreductive surgery (CRS) has remained an area of significant research interest. The purpose of this review is to provide high-level evidence for regional treatment approaches in the management of GCPC with limited peritoneal disease. METHODS: A review of the current literature and ongoing clinical trials for regional IP therapies for GCPC was performed. Studies included in this review comprise of phase III randomized controlled trials, non-randomized phase II studies, high-impact retrospective studies, and active ongoing clinical trials for each available IP modality. RESULTS: The three common IP approaches are heated intraperitoneal chemotherapy (HIPEC), normothermic intraperitoneal chemotherapy (NIPEC) and more recently introduced, pressurized intraperitoneal aerosolized chemotherapy (PIPAC). These IP approaches have been combined with systemic therapy and/or CRS with varying degrees of promising results, demonstrating evidence of improvements in survival rates and peritoneal disease control. Patient selection, optimization of systemic therapy, and completeness of cytoreduction have emerged as major factors influencing the design of contemporary and ongoing trials. CONCLUSION: IP chemotherapy has a clear role in the management of patients with GCPC, and when combined with CRS in appropriately selected patients has the potential to significantly improve survival. Ongoing and upcoming IP therapy clinical trials hold great promise to shape the treatment paradigm for GCPC.

Neurosurgery compared to orthopedic spine consultation: A single level I trauma center experience.

Introduction: Both Orthopedic Surgery (OS) and Neurosurgery (NS) perform spine surgery in the setting of trauma. However, it is unknown whether outcomes differ between these specialties. This study compares management and outcomes for vertebral fractures between NS and OS, hypothesizing similar operation rate, length of stay (LOS), and readmission. Research question: Do outcomes differ between NS and OS in the management of vertebral fractures following trauma? Methods: A retrospective single-center study was conducted on adult patients with cervical, thoracic, lumbar, and sacral fractures treated at a single trauma center, where no standardized pathway exists across NS and OS. Patients were compared for injury profile, diagnostic imaging, and operative techniques as well as LOS, mortality, and complications. Results: A total of 630 vertebral fracture patients (OS:350 (55.6%); NS:280 (44.4%)) were included. NS utilized magnetic resonance imaging (MRI) more commonly (36.4% vs. 22.6%, p < 0.001). NS patients more often underwent operation (13.2% vs. 7.4%, p = 0.016) despite similar fracture number and severity (p > 0.05). Post-operative complications, LOS, and readmission rates were similar between cohorts (p > 0.05). Discussion and conclusion: Despite similar injury profiles, NS had higher rates of MRI usage and operative interventions in the context of traumatic spine fractures. Despite differences in management, major clinical outcomes were similar between NS and OS. However, we do call for further standardization of evaluation and treatment of patients based on established algorithms from such as the AOSpine Thoracolumbar Spine Injury Classification System (ATLICS).

Is primary breast melanoma a true pathological entity? The argument against it.

Background: Previous studies have reported cases of primary melanoma of the breast parenchyma (PMBP), but the pathogenesis of this disease remains poorly understood. We review the presentation and outcomes of reported cases and provide detailed pathological analysis of four additional cases. Furthermore, we discuss potential theories regarding the pathogenesis of this clinical presentation. Results: We identified 29 published studies (n = 95 patients) and report four new cases (n = 99). Ninety-one (92 %) patients were female, with a median age of 50 years. Previous skin melanomas were reported by 56 % of patients, with the trunk being the most common location (32.7 %) followed by the upper extremities (20 %). The most common tumor location reported (n = 73) was the right (49 %) upper outer quadrant (56 %). The median time from skin melanoma diagnosis to the presence of a breast mass was 65 months (1-192). Nodal status at presentation was reported in n = 67 (68 %) patients. Of these, positive nodal metastases were seen in 40.3 %, while distant metastatic disease at presentation was reported in 30 % of patients. Surgery was performed in 66 %, being partial mastectomy (PM) the most common procedure in 82 %. Adjuvant therapy was described in 38 patients. The reported (n = 12) median survival was 11.5 (1-70) months. Conclusion: Melanomas identified in the breast parenchyma are likely the result of nodal or hematogenous spread from previously known or unknown melanomas, and should not be considered as PMBP. Management should be multidisciplinary, including surgical excision aimed at obtaining negative margins with lymphadenectomy of clinically positive nodes and neoadjuvant/adjuvant immunotherapy.

The Utility of Transcranial Electrical Stimulation Motor Evoked Potential Monitoring in Predicting Postoperative Supplementary Motor Area Syndrome and Motor Function Recovery.

BACKGROUND: Postoperative hemiparesis following frontal lobe lesion resection is alarming, and predicting motor function recovery is challenging. Supplementary motor area (SMA) syndrome following resection of frontal lobe lesions is often indistinguishable from postoperative motor deficit due to surgical injury of motor tracts. We aimed to describe the use of intraoperative transcranial electrical stimulation (TES) with motor evoked potential monitoring data as a diagnostic tool to distinguish between SMA syndrome and permanent motor deficit (PMD). METHODS: A retrospective analysis of 235 patients undergoing craniotomy and resection with TES-MEP monitoring for a frontal lobe lesion was performed. Patients who developed immediate postoperative motor deficit were included. Motor deficit and TES-MEP findings were categorized by muscle group as left upper extremity, left lower extremity, right upper extremity, or right lower extremity. Statistical analysis was performed to determine the predictive value of stable TES-MEP for SMA syndrome versus PMD. RESULTS: This study included 20 patients comprising 29 cases of immediate postoperative motor deficit by muscle group. Of these, 27 cases resolved and were diagnosed as SMA syndrome, and 2 cases progressed to PMD. TES-MEP stability was significantly associated with diagnosis of SMA syndrome (P = 0.015). TES-MEP showed excellent diagnostic utility with a sensitivity and positive predictive value of 100% and 92.6%, respectively. Negative predictive value was 100%. CONCLUSIONS: Temporary SMA syndrome is difficult to distinguish from PMD immediately postoperatively. TES-MEP may be a useful intraoperative adjunct that may aid in distinguishing SMA syndrome from PMD secondary to surgical injury.

A Systematic Review of Short-Term Outcomes of Minimally Invasive Thoracoscopic Surgery for Lung Cancer after Neoadjuvant Systemic Therapy.

BACKGROUND: Minimally invasive surgeries for non-small cell lung cancers (NSCLCs) such as video-assisted thoracoscopic surgeries (VATSs) and robotic-assisted thoracoscopic surgeries (RATSs) have become standard of care for patients needing surgical resection in early stages. The role for neoadjuvant systemic therapy has increased with patients receiving neoadjuvant systemic chemotherapy and immunotherapy. However, there has been some equipoise over the intraoperative and overall outcomes for these patients. Here, we review the current data regarding outcomes of patients undergoing minimally invasive thoracic surgical resection after systemic chemotherapy, immunotherapy, or both. METHODS: A systematic literature review of randomized controlled trials and observational studies presenting data on patients with NSCLC that underwent neoadjuvant systemic therapy followed by minimally invasive surgery was performed assessing complications, conversion rates, and lymph node yield. RESULTS: Our search strategy and review of references resulted in 239 publications to screen with 88 full texts assessed and 21 studies included in our final review. VATS had a statistically significant higher lymph node yield in five studies. The reported conversion rates ranged from 0 to 54%. Dense adhesions, bleeding, and difficult anatomy were the most common reported reasons for conversion to open surgeries. The most common complications between both groups were prolonged air leak, arrythmia, and pneumonia. VATS was found to have significantly fewer complications in three papers. CONCLUSIONS: The current literature supports VATS as safe and feasible for patients with NSCLC after neoadjuvant systemic treatment. Surgeons should remain prepared to convert to open surgeries in those patients with dense adhesions and bleeding risk.

The Cost of Gunshot Wounds to the Head: An Unevenly Distributed Burden.

BACKGROUND: Despite the significant clinical consequences and socioeconomic costs of gunshot wounds to the head (GSWH), studies examining prehospital risk factors, geospatial patterns, and economic cost are lacking. METHODS: A retrospective analysis was performed for patients with GSWH (single or multiple injuries) presenting to the level one Ryder Trauma Center (hospital patients) as well as the Miami-Dade County Medical Examiner (ME) Department, from October 2013 to October 2015. In addition, ME data were queried from the previous decade (2008-2017) to analyze longitudinal trends. RESULTS: A total of 402 consecutive patients met the inclusion criteria: 297 (74%) presented to the ME and 105 (26%) presented to the hospital. GSWH in our cohort had a case fatality rate of 89%, predominantly affecting males, whites, and individuals who committed suicide, with a mean age of 41.9 ± 20.6 years. Hospital patients were more likely to be black males from low socioeconomic status (SES) regions involved in assault. Older white males were overrepresented in patients attempting and completing suicide and thus comprised a higher percentage of ME cases. Geospatial analysis of hospital patient injury zip codes shows that GSWH are significantly clustered in low-income urban centers with greater poverty rates. In Miami-Dade County, the economic burden of GSWH, as measured by total health care costs and lifetime productivity losses, was estimated to be $11,867,415 and $246,179,498, respectively. CONCLUSIONS: In the first analysis of GSWH with the inclusion of both hospital and ME data in a representative urban setting, our findings show prehospital risk factors and the unequal distribution of the significant economic costs of GSWH.

A Simple Risk Score to Predict Clavien-Dindo Grade IV and V Complications After Non-elective Cholecystectomy.

BACKGROUND: Non-elective cholecystectomies can lead to severe postoperative complications and mortality. Existing risk prediction tools do not meet the need to reliably predict these complications. METHODS: Using the 2011-2016 American College of Surgeons National Surgical Quality Improvement Program datasets, we identified patients undergoing non-elective cholecystectomy with primary ICD 9/10 codes indicating the following diagnoses: symptomatic cholelithiasis, acute cholecystitis, choledocholithiasis, gallstone pancreatitis, and cholangitis. We randomly allocated patients to derivation and validation cohorts (80/20 split). Severe complications (Clavien-Dindo grades IV and V) included unplanned intubation, prolonged mechanical ventilation, pulmonary embolism, acute renal failure requiring dialysis, stroke, myocardial infarction, cardiac arrest, septic shock, and mortality. Logistic regression using backward selection identified predictors of severe complications and a risk score was generated based on this model. RESULTS: Of 68,953 patients in the derivation cohort, 1.7% (N = 1157) suffered severe complications. The final multivariable risk score model included the following predictors: age (0-12 points), preoperative sepsis (5 points), planned open procedure (5 points), estimated glomerular filtration rate (0-13 points), and preoperative albumin level (0-8 points). The associated risk-score model yielded scores from 0 to 43 with 0.1-59.4% predicted probability of severe complications and had a C-statistic of 0.845 (95% CI 0.834, 0.857) in the derivation cohort and 0.870 (95% CI 0.851, 0.889) in the validation cohort. CONCLUSION: A simple risk-score model predicts severe complications in patients undergoing unplanned cholecystectomy for common indications encountered in an acute care surgery service and identifies high-risk patients.

Characteristics and Outcomes of Women With COVID-19 Giving Birth at US Academic Centers During the COVID-19 Pandemic.

Importance: Prior studies on COVID-19 and pregnancy have reported higher rates of cesarean delivery and preterm birth and increased morbidity and mortality. Additional data encompassing a longer time period are needed. Objective: To examine characteristics and outcomes of a large US cohort of women who underwent childbirth with vs without COVID-19. Design, Setting, and Participants: This cohort study compared characteristics and outcomes of women (age ≥18 years) who underwent childbirth with vs without COVID-19 between March 1, 2020, and February 28, 2021, at 499 US academic medical centers or community affiliates. Follow-up was limited to in-hospital course and discharge destination. Childbirth was defined by clinical classification software procedural codes of 134-137. A diagnosis of COVID-19 was identified using International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) diagnosis of U07.1. Data were analyzed from April 1 to April 30, 2021. Exposures: The presence of a COVID-19 diagnosis using ICD-10. Main Outcomes and Measures: Analyses compared demographic characteristics, gestational age, and comorbidities. The primary outcome was in-hospital mortality. Secondary outcomes included hospital length of stay, intensive care unit (ICU) admission, mechanical ventilation, and discharge status. Continuous variables were analyzed using t test, and categorical variables were analyzed using χ2. Results: Among 869 079 women, 18 715 (2.2%) had COVID-19, and 850 364 (97.8%) did not. Most women were aged 18 to 30 years (11 550 women with COVID-19 [61.7%]; 447 534 women without COVID-19 [52.6%]) and were White (8060 White women [43.1%] in the COVID-19 cohort; 499 501 White women (58.7%) in the non-COVID-19 cohort). There was no significant increase in cesarean delivery among women with COVID-19 (6088 women [32.5%] vs 273 810 women [32.3%]; P = .57). Women with COVID-19 were more likely to have preterm birth (3072 women [16.4%] vs 97 967 women [11.5%]; P < .001). Women giving birth with COVID-19, compared with women without COVID-19, had significantly higher rates of ICU admission (977 women [5.2%] vs 7943 women [0.9%]; odds ratio [OR], 5.84 [95% CI, 5.46-6.25]; P < .001), respiratory intubation and mechanical ventilation (275 women [1.5%] vs 884 women [0.1%]; OR, 14.33 [95% CI, 12.50-16.42]; P < .001), and in-hospital mortality (24 women [0.1%] vs 71 [<0.01%]; OR, 15.38 [95% CI, 9.68-24.43]; P < .001). Conclusions and Relevance: This retrospective cohort study found that women with COVID-19 giving birth had higher rates of mortality, intubation, ICU admission, and preterm birth than women without COVID-19.

CIC-rearranged round cell (Ewing-like) sarcoma of the uterus: Review of the literature.

CIC-rearranged round cell sarcoma (CRS) is a rare entity that presents in various anatomical locations and involves deep soft-tissue structures and skin. Although commonly confused with and clinically similar to Ewing sarcoma (ES), investigators have recently shown that this unique condition maintains morphologic and pathologic features that are distinct from ES. In this report, we present and discuss a case of CRS of the uterus, the first of its kind to be reported in the English-language literature. We urge the scientific community to continue its investigations in elucidating the features of this entity, as young women who suffer from this condition have dismal prognoses and currently do not have access to therapeutic options for cure.

Utility of diagnostic cerebral angiography in the management of suspected central nervous system vasculitis.

Vasculitis of the central nervous system is a rare and poorly understood disease of the brain and spinal cord. Cerebral angiography is the radiological gold standard for diagnosis in patients with compatible clinical findings. However, advances in the quality of noninvasive neuroimaging techniques of cerebral and spinal vasculature such as magnetic resonance angiography (MRA) and computed tomography angiography (CTA) may obviate the need for invasive catheter angiography. We reviewed our institutional experience at Jackson Memorial Hospital between 2011 and 2016 to assess the utility of performing a cerebral digital subtraction angiogram (DSA) in the management of suspected vasculitis. In 16 (59%) of the 27 patients who underwent both noninvasive imaging and DSA, neither imaging studies showed any evidence of vasculitis. Despite these negative studies, 2 patients were treated empirically with immunosuppressants based on clinical symptoms and laboratory findings. 10 (37%) patients demonstrated irregularities on MRA and findings were confirmed by DSA in 6 of these patients. All 6 of these patients were treated, however, 2 of the 4 patients with abnormal MRA and normal DSA were also started on immunosuppressive therapy despite negative DSA. In conclusion, invasive catheter-based angiography may be of limited benefit in the diagnosis and management of PCNSV when considered in the context of clinical and laboratory findings and MRA or CTA results. Further large studies are necessary to determine whether non-invasive imaging can replace DSA.

Neurosurgical management of Currarino syndrome: A case series and review of literature.

BACKGROUND: The Currarino syndrome (CS), defined by the triad of anorectal malformations, sacral bone deformities, and presacral masses, is rare. There are few surgical series that discuss conservative management versus the surgical approaches to these lesions. Here, we describe utilizing a combined anterior and posterior approach for resecting these lesions in four patients. METHODS: Four patients with CS were treated with two-stage approaches performed by a multidisciplinary team, including pediatric neurosurgery and general surgery. The first anterior laparoscopic approach mobilized the presacral mass from its ventral attachments. The second posterior procedure detethered the spinal cord, repaired the dural defect, and facilitated removal of the presacral mass. RESULTS: Gross total resection of all four presacral masses was accomplished without intraoperative complication; all patients clinically improved. CONCLUSION: The CS is characterized by a large presacral mass. Here, one must rule out malignancy and also consider diagnosis/resection due to the risks for malignant transformation. The operative approach we described in four patients utilized standard anterior mobilization of the mass, followed by posterior detethering, dural repair, and ultimate resection.

Intrathecal baclofen versus selective dorsal rhizotomy for children with cerebral palsy who are nonambulant: a systematic review.

OBJECTIVE: Cerebral palsy (CP) is the most common childhood physical disability. Historically, children with hypertonia who are nonambulatory (Gross Motor Function Classification System [GMFCS] level IV or V) were considered candidates for intrathecal baclofen (ITB) therapy to facilitate care and mitigate discomfort. Selective dorsal rhizotomy (SDR) was often reserved for ambulant children to improve gait. Recently, case series have suggested SDR as an alternative to ITB in selected children functioning at GMFCS level IV/V. The objective for this study was to systematically review the evidence for ITB and SDR in GMFCS level IV or V children. METHODS: Medline, Embase, Web of Science, and Cochrane databases were systematically searched. Articles were screened using the following inclusion criteria: 1) peer-reviewed articles reporting outcomes after SDR or ITB; 2) outcomes reported using a quantifiable scale or standardized outcome measure; 3) patients were < 19 years old at the time of operation; 4) patients had a diagnosis of CP; 5) patients were GMFCS level IV/V or results were reported based on GMFCS status and included some GMFCS level IV/V patients; 6) article and/or abstract in English; and 7) primary indication for surgery was hypertonia. Included studies were assessed with the Risk of Bias in Non-Randomized Studies - of Interventions (ROBINS-I) tool. RESULTS: Twenty-seven studies met inclusion criteria. The most commonly reported outcomes were spasticity (on the Mean Ashworth Scale) and gross motor function (using the Gross Motor Function Measure), although other outcomes including frequency of orthopedic procedures and complications were also reported. There is evidence from case series that suggests that both ITB and SDR can lower spasticity and improve gross motor function in this nonambulatory population. Complication rates are decidedly higher after ITB due in part to the ongoing risk of device-related complications. The heterogeneity among study design, patient selection, outcome selection, and follow-up periods was extremely high, preventing meta-analysis. There are no comparative studies, and meaningful health-related quality of life outcomes such as care and comfort are lacking. This review is limited by the high risk of bias among included studies. Studies of SDR or ITB that did not clearly describe patients as being GMFCS level IV/V or nonambulatory were excluded. CONCLUSIONS: There is a lack of evidence comparing the outcomes of ITB and SDR in the nonambulatory CP population. This could be overcome with standardized prospective studies using more robust methodology and relevant outcome measures.

Expression of PD-1 by T Cells in Malignant Glioma Patients Reflects Exhaustion and Activation.

PURPOSE: Glioblastoma (GBM) is the most common primary malignant tumor in the central nervous system. Our recent preclinical work has suggested that PD-1/PD-L1 plays an important immunoregulatory role to limit effective antitumor T-cell responses induced by active immunotherapy. However, little is known about the functional role that PD-1 plays on human T lymphocytes in patients with malignant glioma.Experimental Design: In this study, we examined the immune landscape and function of PD-1 expression by T cells from tumor and peripheral blood in patients with malignant glioma. RESULTS: We found several differences between PD-1+ tumor-infiltrating lymphocytes (TIL) and patient-matched PD-1+ peripheral blood T lymphocytes. Phenotypically, PD-1+ TILs exhibited higher expression of markers of activation and exhaustion than peripheral blood PD-1+ T cells, which instead had increased markers of memory. A comparison of the T-cell receptor variable chain populations revealed decreased diversity in T cells that expressed PD-1, regardless of the location obtained. Functionally, peripheral blood PD-1+ T cells had a significantly increased proliferative capacity upon activation compared with PD-1- T cells. CONCLUSIONS: Our evidence suggests that PD-1 expression in patients with glioma reflects chronically activated effector T cells that display hallmarks of memory and exhaustion depending on its anatomic location. The decreased diversity in PD-1+ T cells suggests that the PD-1-expressing population has a narrower range of cognate antigen targets compared with the PD-1 nonexpression population. This information can be used to inform how we interpret immune responses to PD-1-blocking therapies or other immunotherapies.