Apraxia of speech with phonological alexia and agraphia following resection of the left middle precentral gyrus: illustrative case.

BACKGROUND: Apraxia of speech is a disorder of speech-motor planning in which articulation is effortful and error-prone despite normal strength of the articulators. Phonological alexia and agraphia are disorders of reading and writing disproportionately affecting unfamiliar words. These disorders are almost always accompanied by aphasia. OBSERVATIONS: A 36-year-old woman underwent resection of a grade IV astrocytoma based in the left middle precentral gyrus, including a cortical site associated with speech arrest during electrocortical stimulation mapping. Following surgery, she exhibited moderate apraxia of speech and difficulty with reading and spelling, both of which improved but persisted 6 months after surgery. A battery of speech and language assessments was administered, revealing preserved comprehension, naming, cognition, and orofacial praxis, with largely isolated deficits in speech-motor planning and the spelling and reading of nonwords. LESSONS: This case describes a specific constellation of speech-motor and written language symptoms-apraxia of speech, phonological agraphia, and phonological alexia in the absence of aphasia-which the authors theorize may be attributable to disruption of a single process of "motor-phonological sequencing." The middle precentral gyrus may play an important role in the planning of motorically complex phonological sequences for production, independent of output modality.

Not All Patients With Locally Advanced Rectal Cancer Benefit From Neoadjuvant Therapy.

BACKGROUND: While neoadjuvant combined modality therapy (NA-CMT) is beneficial for most patients with locally advanced rectal cancer some patients may experience disease progression during treatment. The purpose of this study is to identify characteristics associated with progression during NA-CMT. METHODS: A single institution retrospective review of patients with stage II-III rectal cancer receiving NA-CMT was conducted from 2008-2019. Patients with incomplete or unknown NA-CMT treatment and those who received chemotherapy in addition to NA-CMT were excluded. Initial staging MRI was compared to post-operative pathology to determine progression. Definitions: responders (complete response or regression) and non-responders (stable disease or progression). RESULTS: 156 patients were included: 25 (16.1%) complete responders, 79 (50.6%) had evidence of regression, 34 (21.8%) were stable non-responders, and 18 (11.5%) were progressors. Those who progressed had worse overall survival. Factors associated with non-responders included black race (OR 4.5, 95% CI: 1.10-18.7) and increasing distance from the anal verge (OR 1.2, 95% CI: .2-2.9). Distance from the anal verge was determined via MRI. Recurrence was significantly more common among non-responders (15, 30.61%) when compared to responders (14, 13.46%), P = .012. CONCLUSION: Patients who progress despite NA-CMT have overall worse survival compared to patients who do respond. While this study failed to identify modifiable or predictive risk factors for progression, the multivariate logistic regression model suggests that race and tumor biology may play a role in progression. Future studies should focus on early identification of patients who may not benefit from NA-CMT in an effort to develop alternative treatment algorithms.

Comparing Donor Site Morbidity for Autologous Breast Reconstruction: Thigh vs. Abdomen.

Although abdominally-based free flaps have long been the gold standard, the profunda artery perforator (PAP) flap has emerged as an important alternative option for autologous breast reconstruction. The aim of this study was to directly compare the donor site morbidity of using the PAP versus deep inferior epigastric perforator (DIEP) free flap. Methods: We performed a retrospective review of patients undergoing autologous breast reconstruction using a DIEP and/or PAP flap from January 2017 to December 2020. In total, 30 PAP flap patients were matched with 60 DIEP flap patients. Outcomes included donor site wound dehiscence, length of stay, narcotic consumption, and pain scores. Patient-reported outcomes for the thigh versus abdomen were compared using questions derived from the BREAST-Q. Results: There was no significant difference in length of stay (P = 0.182), reoperation rates (P = 0.999), flap failure rates (P = 0.999), or donor site complications (P = 0.999). Both groups had similar mean pain scores, maximum pain scores, daily and total narcotic requirements. In comparing the thigh or abdomen as a donor site, there was no difference in frequency of negative symptoms (difficulty with daily activities, discomfort, tightness, and negative impact on ability to work) or satisfaction scores as related to their appearance in and out of clothing and the appearance of the scar. Conclusions: The thigh and abdomen are both suitable donor sites for autologous breast reconstruction with similar flap-related and patient-reported outcomes. The ultimate decision regarding whether to use a PAP or DIEP flap for breast reconstruction should be tailored based on patient anatomy and preference.

Free Flap Reconstruction of Posterior Trunk Soft-Tissue Defects: Single-Institution Experience and Systematic Literature Review.

BACKGROUND: The posterior trunk is a technically demanding location for microvascular free tissue transfer. In this study, the authors report their own institutional experience with soft-tissue free flap reconstruction of the posterior trunk and provide a systematic review of the literature regarding this uncommon clinical scenario. METHODS: A systematic review was performed using the PubMed database in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A single-institution retrospective review was also performed including all patients who received a soft-tissue free flap for a posterior trunk defect between 1990 and 2019. RESULTS: The database search yielded 15 articles, representing 61 patients; the most commonly used flap was the latissimus dorsi (45.9 percent) and the most commonly reported defect location was the lumbosacrum (42.3 percent). Retrospective review of the authors' database identified 26 patients, with the latissimus dorsi being the most common flap and the sacrum the most common defect site. The authors' institutional case series showed a 30.7 percent major complication rate and 7.7 percent total flap loss rate; 38.4 percent of flaps required vein grafting. CONCLUSIONS: In this study, the authors provided a systematic literature review and described their own long-term institutional experience with these rare and difficult reconstructions. Although the overall complication rate is high, these reconstructions are frequently necessary, and an algorithmic approach can improve outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Perforator Mapping of the Profunda Artery Perforator Flap: Anatomy and Clinical Experience.

BACKGROUND: Discovering alternatives to workhorse flaps that have more consistent anatomy and lower donor-site morbidity has become a focus of reconstructive surgery research. This study provides a simplified approach to profunda artery perforator flap design and harvest based on reliable anatomical landmarks. METHODS: A retrospective review was conducted of 70 patients who underwent 83 profunda artery perforator flap reconstructions for postoncologic defects from 2016 to 2018. The authors recorded and analyzed the profunda artery perforator flap sizes and clinical applications, the numbers and locations of the perforators, and the patient outcomes. RESULTS: Most of the profunda artery perforator flaps were for head and neck [46 patients (65.7 percent)] and breast [21 patients (30 percent)] reconstructions. Flaps were most commonly based on perforator A (33.7 percent) and perforator B (33.7 percent), followed by perforators B and C combined (18.1 percent). Perforators were located a mean of 7.5 cm (perforator A), 12.7 cm (B), and 17.6 cm (C) distal to the pubic tubercle parallel to the axis between the pubic tubercle and the medial femoral condyle and 7.9 cm (A), 7.3 cm (B), and 6.1 cm (C) posterior from the axis. There was no flap loss. One patient underwent successful salvage surgery after arterial flap thrombosis. Eight patients (9.6 percent) developed superficial wound dehiscence that was managed conservatively. CONCLUSIONS: Perforator mapping demonstrated consistent anatomical locations of sizeable profunda artery perforators in the inner thigh. Along with its consistent and robust vascular anatomy and minimal donor-site morbidity, the profunda artery perforator flap's volume and pliability make it a reliable option for soft-tissue reconstruction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

The impact of sarcopenia on oncologic abdominal wall reconstruction.

BACKGROUND AND OBJECTIVES: Sarcopenia is an objective measure of patient frailty and is a predictor of adverse surgical outcomes. We hypothesized that sarcopenia is associated with increased surgical site occurrence (SSO) and hernia occurrences in patients undergoing oncologic abdominal wall reconstruction. METHODS: Consecutive patients who underwent abdominal wall reconstruction (AWR) for an abdominal wall ablative defect at a single center from 2005 to 2015 were evaluated. The total psoas index (TPI) was used to define sarcopenia. The primary endpoint of the study was hernia occurrence; (SSO) was a secondary outcome measure. RESULTS: Eighty-six patients met the inclusion criteria. Multivariate analysis demonstrated that sarcopenia increased the risk of hernia more than threefold, trending toward significance (OR = 3.3; 95% CI: 0.69-15.4; P = .13). Multivariate logistic regression demonstrated that preoperative radiotherapy (OR = 4.8, 95% CI: 1.4-16; P = .01) and obesity (OR = 4.9, 95% CI: 1.5-16.3; P =.009) were independent predictors of developing an SSO. CONCLUSIONS: Sarcopenia, as defined by TPI, is correlated with hernia occurrence, but not SSO. These findings emphasize the importance of preoperative fitness and nutritional optimization and provide useful information for preoperative counseling and risk stratification.

The effect of sarcopenia on perioperative complications in abdominally based free-flap breast reconstruction.

PURPOSE: The identification of patient-specific risk factors, which predict morbidity following abdominally based microvascular breast reconstruction is difficult. Sarcopenia is a proxy for patient frailty and is an independent predictor of complications in a myriad of surgical disciplines. We predict that sarcopenic patients will be at higher risk for surgical complications following abdominally based microvascular breast reconstruction. METHODS: A retrospective study of all patients who underwent delayed abdominally based autologous breast reconstruction following postmastectomy radiation therapy from 2007 to 2013 at a single institution was conducted. Univariate and multiple logistic regression models were used to assess the effect of sarcopenia on postoperative outcomes. RESULTS: Two hundred and eight patients met the inclusion criteria, of which 30 met criteria for sarcopenia (14.1%). There were no significant differences in demographics between groups. There were no significant differences in minor (36.7% vs 44.4%; P = .43) or major (16.7% vs 25.3%; P = .36) complications between groups as well as hospital length of stay. Multivariable logistic regression demonstrated that a staged reconstruction with the use of a tissue expander was the only consistent variable, which predicted major complications (OR, 2.24; 95% CI, 1.18-4.64; P = .015). CONCLUSIONS: Sarcopenia does not predispose to minor or major surgical complications in patients who undergo abdominally based microsurgical breast reconstruction.

Ex vivo biomechanical characterization of syringe-needle ejections for intracerebral cell delivery.

Intracerebral implantation of cell suspensions is finding its clinical translation with encouraging results in patients with stroke. However, the survival of cells in the brain remains poor. Although the biological potential of neural stem cells (NSCs) is widely documented, the biomechanical effects of delivering cells through a syringe-needle remain poorly understood. We here detailed the biomechanical forces (pressure, shear stress) that cells are exposed to during ejection through different sized needles (20G, 26G, 32G) and syringes (10, 50, 250 µL) at relevant flow rates (1, 5, 10 µL/min). A comparison of 3 vehicles, Phosphate Buffered Saline (PBS), Hypothermosol (HTS), and Pluronic, indicated that less viscous vehicles are favorable for suspension with a high cell volume fraction to minimize sedimentation. Higher suspension viscosity was associated with greater shear stress. Higher flow rates with viscous vehicle, such as HTS reduced viability by ~10% and also produced more apoptotic cells (28%). At 5 µL/min ejection using a 26G needle increased neuronal differentiation for PBS and HTS suspensions. These results reveal the biological impact of biomechanical forces in the cell delivery process. Appropriate engineering strategies can be considered to mitigate these effects to ensure the efficacious translation of this promising therapy.

Long-term retention of ECM hydrogel after implantation into a sub-acute stroke cavity reduces lesion volume.

Salvaging or functional replacement of damaged tissue caused by stroke in the brain remains a major therapeutic challenge. In situ gelation and retention of a hydrogel bioscaffold composed of 8mg/mL extracellular matrix (ECM) can induce a robust invasion of cells within 24h and potentially promote a structural remodeling to replace lost tissue. Herein, we demonstrate a long-term retention of ECM hydrogel within the lesion cavity. A decrease of approximately 32% of ECM volume is observed over 12weeks. Lesion volume, as measured by magnetic resonance imaging and histology, was reduced by 28%, but a battery of behavioral tests (bilateral asymmetry test; footfault; rotameter) did not reveal a therapeutic or detrimental effect of the hydrogel. Glial scarring and peri-infarct astrocytosis were equivalent between untreated and treated animals, potentially indicating that permeation into host tissue is required to exert therapeutic effects. These results reveal a marked difference of biodegradation of ECM hydrogel in the stroke-damaged brain compared to peripheral soft tissue repair. Further exploration of these structure-function relationships is required to achieve a structural remodeling of the implanted hydrogel, as seen in peripheral tissues, to replace lost tissue and promote behavioral recovery. STATEMENT OF SIGNIFICANCE: In situ gelation of ECM is essential for its retention within a tissue cavity. The brain is a unique environment with restricted access that necessitates image-guided delivery through a thin needle to access tissue cavities caused by stroke, as well as other conditions, such as traumatic brain injury or glioma resection. Knowledge about a brain tissue response to implanted hydrogels remains limited, especially in terms of long-term effects and potential impact on behavioral function. We here address the long-term retention of hydrogel within the brain environment, its impact on behavioral function, as well as its ability to reduce further tissue deformation caused by stroke. This study highlights considerable differences in the brain's long-term response to an ECM hydrogel compared to peripheral soft tissue. It underlines the importance of understanding the effect of the structural presence of a hydrogel within a cavity upon host brain tissue and behavioral function. As demonstrated herein, ECM hydrogel can fill a cavity long-term to reduce further progression of the cavity, while potentially serving as a reservoir for local drug or cell delivery.

Immune Reconstitution Inflammatory Syndrome Occurring in a Kidney Transplant Patient with Extrapulmonary Tuberculosis.

Tuberculosis (TB) occurring in solid organ transplantation (SOT) is associated with significant morbidity and mortality usually due to delays in diagnosis, drug toxicity encountered with antimycobacterial therapy, and drug-drug interactions. TB in SOT patients may mimic other infectious and noninfectious posttransplant complications such as posttransplant lymphoproliferative disorder (PTLD) and systemic cytomegalovirus infection. Immune reconstitution inflammatory syndrome (IRIS) is a host response resulting in paradoxical worsening of an infectious disease which occurs after the employment of effective therapy and reversal of an immunosuppressed state. We describe the development of immune reconstitution inflammatory syndrome (IRIS), a unique complication occurring during the treatment of extrapulmonary tuberculosis occurring after transplant which resulted from decreasing immunosuppression in a patient who received Alemtuzumab induction therapy. Although (IRIS) has been originally described in HIV/AIDS patients receiving highly active antiretroviral therapy (HAART), solid organ transplant recipients with diagnosed or occult TB whose immune system may undergo immune reconstitution during their posttransplant course represent a new high risk group.

A Comparison of Exogenous Labels for the Histological Identification of Transplanted Neural Stem Cells.

The interpretation of cell transplantation experiments is often dependent on the presence of an exogenous label for the identification of implanted cells. The exogenous labels Hoechst 33342, 5-bromo-2'-deoxyuridine (BrdU), PKH26, and Qtracker were compared for their labeling efficiency, cellular effects, and reliability to identify a human neural stem cell (hNSC) line implanted intracerebrally into the rat brain. Hoechst 33342 (2 mg/ml) exhibited a delayed cytotoxicity that killed all cells within 7 days. This label was hence not progressed to in vivo studies. PKH26 (5 µM), Qtracker (15 nM), and BrdU (0.2 µM) labeled 100% of the cell population at day 1, although BrdU labeling declined by day 7. BrdU and Qtracker exerted effects on proliferation and differentiation. PKH26 reduced viability and proliferation at day 1, but this normalized by day 7. In an in vitro coculture assay, all labels transferred to unlabeled cells. After transplantation, the reliability of exogenous labels was assessed against the gold standard of a human-specific nuclear antigen (HNA) antibody. BrdU, PKH26, and Qtracker resulted in a very small proportion (<2%) of false positives, but a significant amount of false negatives (∼30%), with little change between 1 and 7 days. Exogenous labels can therefore be reliable to identify transplanted cells without exerting major cellular effects, but validation is required. The interpretation of cell transplantation experiments should be presented in the context of the label's limitations.

Moderately hypoplastic arches: do they reliably grow into adulthood after conventional coarctation repair?

UNLABELLED: To determine whether conventional coarctation repair results in sustained growth of hypoplastic transverse arches, we examined the follow-up of 20 patients operated through a thoracotomy between 1990 and 1995 who had available serial echocardiographic examinations. Mean age at operation was 8.6+/-5.7 days. In the distal transverse arch, maximum change was observed in the early postoperative period and sustained growth was observed thereafter. At last follow-up, no patients had Z-scores of less than -2. In contrast, only minimal growth occurred in the proximal transverse arch (mean Z-score diameter before and after repair: -1.87+/-0.12 vs. -1.66+/-0.09; P=0.05) in the postoperative period. At last follow-up, seven patients (35%) kept a diameter Z-score of less than -2, and 5 of them had a gradient of 15 mmHg (P=0.01). No correlation was found between the size of the proximal arch at last follow-up and its size before repair or technique used. CONCLUSION: Patients with moderately hypoplastic arch treated by conventional coarctation repair have adequate growth of the distal arch demonstrated at long-term follow-up, but one-third of them keep a small proximal arch. This subset of patients is at risk of developing hypertension and may warrant further investigation.

Ginger's (Zingiber officinale Roscoe) inhibition of rat colonic adenocarcinoma cells proliferation and angiogenesis in vitro.

Ginger's (Zingiber officinale Roscoe) natural bioactives, specifically ginger extract and 6-gingerol, were measured for their in vitro inhibition of two key aspects of colon cancer biology--cancer cell proliferation and angiogenic potential of endothelial cell tubule formation. Ginger extract was obtained via column distillation, while the 6-gingerol was purchased from Calbiochem. Antiproliferation activity was assessed through tritiated thymidine ([(3)H]Tdr) incorporation studies of YYT colon cancer cells; the anti-angiogenic ability of gingerol was assessed by a Matrigel assays using MS1 endothelial cells. These selected ginger bioactives had: 1) a direct effect on YYT rat cancer cell proliferation (6-1.5% ginger extract; 100-4 microM 6-gingerol); 2) an indirect effect on MS1 endothelial cell function either at the level of endothelial cell proliferation or through inhibition of MS1 endothelial cell tube formation (100-0.8 microM). Compound 6-gingerol was most effective at lower doses in inhibiting endothelial cell tube formation. These in vitro studies show that 6-gingerol has two types of antitumor effects: 1) direct colon cancer cell growth suppression, and 2) inhibition of the blood supply of the tumor via angiogenesis. Further research is warranted to test 6-gingerol in animal studies as a potential anticancer plant bioactive in the complementary treatment of cancer.

Observed smoking in cars: a method and differences by socioeconomic area.

OBJECTIVES: To establish a reproducible method to estimate he point prevalence of smoking and second-hand smoke (SHS) exposure in cars, and to compare this prevalence between two areas of contrasting socioeconomic status. METHOD: A method involving two teams of observers was developed and evaluated. It involved observing 16,055 cars in Wellington, New Zealand. Two of the observation sites represented a high and a low area of deprivation (based on a neighbourhood deprivation index) and three were in the central city. RESULTS: A 4.1% point prevalence of smoking in cars was observed (95% confidence interval (CI) 3.8% to 4.4%). There was a higher prevalence of smoking in cars in the high deprivation area relative to the other sites, and particularly compared to the low deprivation area (rate ratio relative to the latter 3.2, 95% CI 2.6 to 4.0). Of cars with smoking, 23.7% had other occupants being exposed to SHS. Cars with smoking and other occupants were significantly more likely to have a window open (especially if the smoker was not the driver). The observation method developed was practical, and inter-observer agreement was high (kappa value for the "smoking seen in car" category 0.95). CONCLUSIONS: Observational studies can be an effective way of investigating smoking in cars. The data from this survey suggest that smoking in cars occurs at a higher rate in relatively deprived populations and hence may contribute to health inequalities. Fortunately, there are a number of policy options for reducing SHS exposure in cars including mass media campaigns and laws for smoke-free cars.

The anti-cancer effects of poi (Colocasia esculenta) on colonic adenocarcinoma cells In vitro.

Hawaiians tend to have lower incidence rates of colorectal cancer and it was hypothesized that this may be due to ethnic differences in diet, specifically, their consumption of poi, a starchy paste made from the taro (Colocasia esulenta L.) plant corm. Soluble extracts of poi were incubated at 100 mg/mL in vitro for antiproliferative activity against the rat YYT colon cancer cell line. (3)H-thymidine incorporation studies were conducted to demonstrate that the poi inhibited the proliferation of these cancer cells in a dose-dependent manner. The greatest suppression of YYT colon cancer growth occurred when 25% concentration was used. When poi was incubated with the YYT cells after 2 days, the YYT cells underwent apoptotic changes as evidenced by a positive terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) stain. Poi enhanced the proliferation of normal mouse splenocyte control cells, suggesting that poi is not simply toxic to all cells but even has a positive immunostimulatory role. By flow cytometry, T cells (CD4+ and CD8+) were predominantly activated by the poi. Although numerous factors can contribute to the risk of colon cancer, perhaps poi consumption may contribute to the lower colon cancer rates among Hawaiians by two distinct mechanisms. First, by inducing apoptosis within colon cancer cells; second, by non-specifically activating lymphocytes, which in turn can lyse cancerous cells. Our results suggest for the first time that poi may have novel tumor specific anti-cancer activities and future research is suggested with animal studies and human clinical trials.

Antiangiogenic drugs synergize with a membrane macrophage colony-stimulating factor-based tumor vaccine to therapeutically treat rats with an established malignant intracranial glioma.

Combining a T9/9L glioma vaccine, expressing the membrane form of M-CSF, with a systemic antiangiogenic drug-based therapy theoretically targeted toward growth factor receptors within the tumor's vasculature successfully treated >90% of the rats bearing 7-day-old intracranial T9/9L gliomas. The antiangiogenic drugs included (Z)-3-[4-(dimethylamino)benzylidenyl]indolin-2-one (a platelet-derived growth factor receptor beta and a fibroblast growth factor receptor 1 kinase inhibitor) and oxindole (a vascular endothelial growth factor receptor 2 kinase inhibitor). A total of 20-40% of the animals treated with the antiangiogenic drugs alone survived, while all nontreated controls and tumor vaccine-treated rats died within 40 days. In vitro, these drugs inhibited endothelial cells from proliferating in response to the angiogenic factors produced by T9/9L glioma cells and prevented endothelial cell tubulogenesis. FITC-labeled tomato lectin staining demonstrated fewer and constricted blood vessels within the intracranial tumor after drug therapy. Magnetic resonance imaging demonstrated that the intracranial T9 glioma grew much slower in the presence of these antiangiogenic drugs. These drugs did not affect in vitro glioma cell growth nor T cell mitogenesis. Histological analysis revealed that the tumor destruction occurred at the margins of the tumor, where there was a heavy lymphocytic infiltrate. Real-time PCR showed more IL-2-specific mRNA was present within the gliomas in the vaccinated rats treated with the drugs. Animals that rejected the established T9/9L glioma by the combination therapy proved immune against an intracranial rechallenge by T9/9L glioma, but showed no resistance to an unrelated MADB106 breast cancer.