Hepatic Resection and Transplant in Glycogen Storage Diseases.

Patients with glycogen storage diseases pose unique management challenges to clinicians.These challenges are exacerbated wheneverthey undergo surgery as the basic anomaly in their glycogen storage pathways make them susceptible to organic acidosis, which may in turn complicate their preoperative, intraoperative, and postoperative course. Because of the rarity of these diseases, clinicians may not be aware of the specific management concerns. In the case reported here, a 37-year-old patient with glycogen storage disease type 1 underwentleft hepatectomy for hepatic adenomatosis, which was complicated by intraoperative severe lactic acidosis that was successfully treated. After successful hepatectomy, the patient underwent liver transplant without major lactic acidosis or hemodynamic instability. Early recognition and aggressive management of blood sugar and lactic acidosis in patients with glycogen storage diseases can allow for successful outcomes even when complex surgical procedures are required.

Intraoperative Cardiac Arrest During Adult Liver Transplantation: Incidence and Risk Factor Analysis From 7 Academic Centers in the United States.

BACKGROUND: Intraoperative cardiac arrest (ICA) has a reported frequency of 1 in 10,000 anesthetics but has a much higher estimated incidence in orthotopic liver transplantation (OLT). Single-center studies of ICA in OLT are limited by small sample size that prohibits multivariable regression analysis of risks. METHODS: Utilizing data from 7 academic medical centers, we performed a retrospective, observational study of 5296 adult liver transplant recipients (18-80 years old) between 2000 and 2017 to identify the rate of ICA, associated risk factors, and outcomes. RESULTS: ICA occurred in 196 cases (3.7% 95% confidence interval [CI], 3.2-4.2) and mortality occurred in 62 patients (1.2%). The intraoperative mortality rate was 31.6% in patients who experienced ICA. In a multivariable generalized linear mixed model, ICA was associated with body mass index (BMI) <20 (odds ratio [OR]: 2.04, 95% CI, 1.05-3.98; P = .0386), BMI ≥40 (2.16 [1.12-4.19]; P = .022), Model for End-Stage Liver Disease (MELD) score: (MELD 30-39: 1.75 [1.09-2.79], P = .02; MELD ≥40: 2.73 [1.53-4.85], P = .001), postreperfusion syndrome (PRS) (3.83 [2.75-5.34], P < .001), living donors (2.13 [1.16-3.89], P = .014), and reoperation (1.87 [1.13-3.11], P = .015). Overall 30-day and 1-year mortality were 4.18% and 11.0%, respectively. After ICA, 30-day and 1-year mortality were 43.9% and 52%, respectively, compared to 2.6% and 9.3% without ICA. CONCLUSIONS: We established a 3.7% incidence of ICA and a 1.2% incidence of intraoperative mortality in liver transplantation and confirmed previously identified risk factors for ICA including BMI, MELD score, PRS, and reoperation and identified new risk factors including living donor and length of surgery in this multicenter retrospective cohort. ICA, while rare, is associated with high intraoperative mortality, and future research must focus on therapy to reduce the incidence of ICA.

Examination of sulfonamide-based inhibitors of MMP3 using the conditioned media of invasive glioma cells.

Glioblastoma multiforme (GBM) is the deadliest and the most common primary malignant brain tumour. The median survival for patients with GBM is around one year due to the nature of glioma cells to diffusely invade that make the complete surgical resection of tumours difficult. Based upon the connexin43 (Cx43) model of glioma migration we have developed a computational framework to evaluate MMP inhibition in materials relevant to GBM. Using the ilomastat Leu-Trp backbone, we have synthesised novel sulphonamides and monitored the performance of these compounds in conditioned media expressing MMP3. From the results discussed herein we demonstrate the performance of sulfonamide based MMPIs included AP-3, AP-6, and AP-7.

Mild hypothermia is associated with improved outcomes in patients undergoing microvascular head and neck reconstruction.

OBJECTIVE: Microvascular free tissue transfer has become the standard for reconstruction for large defects. With long operative times and an increased surface area exposed, transient hypothermia is common, but it is unclear how this impacts surgical outcomes. This study evaluated the impact of core body temperature on free tissue flap outcomes in patients undergoing microvascular reconstruction. STUDY DESIGN: Retrospective data analysis. SETTING: Mount Sinai Hospital; NYC, NY; 2007-2016. SUBJECTS AND METHODS: Demographic information, mean/minimum/maximum body temperatures, and the presence of flap complications (venous thrombosis, arterial insufficiency, flap death, wound infection/dehiscence, fistula, chyle leak, hematoma/seroma) of 519 free tissue transfer patients were documented. Binomial logistic regression was used to examine associations between the presence of flap complications and mean temperature. Statistical analysis used SPSS, with p-values ≤0.05 deemed statistically significant. RESULTS: 393 soft-tissue and 125 osteocutaneous flaps were included. 19.8% (n = 103) patients had the presence of ≥1 flap complication, while 80.2% (n = 416) did not. Average temperature for all patients was 36.12 ±â€¯0.84 °C, with minimum at 34.43 ±â€¯0.97 °C and maximum at 37.24 ±â€¯1.23 °C. After controlling for several factors including: tumor stage, radiation, diabetes, BMI, age, sex, and flap type, there was a significant association between flap complications and mean intraoperative temperature (Exp(B) = 1.559, p = 0.004). CONCLUSION: Higher intraoperative temperatures were associated with worse outcomes. A mild relative hypothermia may improve flap outcomes in this population. This represents the largest study to date evaluating the impact of intraoperative temperature on free tissue transfer outcomes.

Intrathecal Morphine Administration Does Not Affect Survival After Liver Resection for Hepatocellular Carcinoma.

Introduction. Opioids may influence tumor recurrence and cancer-free survival in hepatocellular carcinoma (HCC). The relationship between intrathecal morphine administration, tumor recurrence, and patient survival after hepatectomy for HCC is unknown. Patients and Methods. This single-center, retrospective study included 1837 liver resections between July 2002 and December 2012; 410 cases were incorporated in the final univariate and multivariate analysis. Confirmatory propensity matching yielded 65 matched pairs (intrathecal morphine vs none). Primary outcomes were recurrence of HCC and survival. Secondary outcomes included characterization of factors associated with recurrence and survival. Results. Groups were similar except for increased coronary artery disease in the no intrathecal morphine group. All patients received volatile anesthesia. Compared with no intrathecal morphine (N = 307), intrathecal morphine (N = 103) was associated with decreased intraoperative intravenous morphine administration (median difference = 12.5 mg; 95% confidence interval [CI] = 5-20 mg). There was no difference in blood loss, transfusion, 3- or 5-year survival, or recurrence in the univariate analysis. Multivariate analysis identified covariates that significantly correlated with 5-year survival: intrathecal morphine (hazard ratio [HR] = 0.527, 95% CI = 0.296-0.939), lesion diameter (HR = 1.099, 95% CI = 1.060-1.141), vascular invasion (HR = 1.658, 95% CI = 1.178-2.334), and satellite lesions (HR = 2.238, 95% CI = 1.447-3.463). Survival analysis on the propensity-matched pairs did not demonstrate a difference in 5-year recurrence or survival. Discussion and Conclusion. Multivariate analysis revealed a significant association between intrathecal morphine and 5-year survival. This association did not persist after propensity matching. The association between intrathecal morphine and HCC recurrence and survival remains unclear and prospective work is necessary to determine whether an association exists.

Volume at First Leak Is Associated With Sling Failure Among Women With Stress Urinary Incontinence.

INTRODUCTION: Stress urinary incontinence at a low bladder volume is a clinically observed phenomenon that is not well studied with regard to treatment outcomes. The primary aim of our study was to determine if the volume at first leak is associated with sling outcome. METHODS: This is a retrospective cohort study evaluating whether urodynamic stress urinary incontinence observed at low volumes is associated with sling failure using the Synthetic Derivative database. Sling failure was defined as (1) undergoing a subsequent surgery for stress incontinence (eg, urethral bulking agent, repeat sling) or (2) leakage that was subjectively worse or unchanged from baseline. Sling success was defined as subjective improvement in incontinence or being dry. Intrinsic sphincter deficiency was defined as maximum urethral closure pressure 20 cm H20 or less or abdominal leak point pressure less than 60 cm H20. RESULTS: Outcome data were available for 168 of 206 women who underwent a sling after urodynamic testing from 2006 to 2014. Of the 168 women, 80 were transobturator, 79 were retropubic, 8 lacked data regarding the approach to the midurethral sling, and 1 was an autologous pubovaginal sling. Similar failure rates were seen for transobturator (10%) and retropubic slings (7.6%). Preoperative urodynamic parameters, such as cystometric capacity and intrinsic sphincter deficiency, were similar among failed and successful slings. For every additional 50 mL in bladder volume at first leak (SUIvol), there was a 1.6 increased odds of having a successful sling (odds ratio, 1.576; 95% confidence interval, 1.014-2.450; P = 0.04). There was no statistically significant association between maximum urethral closure pressure, abdominal leak point pressure, body mass index, age, sling type, or whether a prior anti-incontinence procedure had been performed and sling success. CONCLUSIONS: Bladder volume at first leak is a strong predictor of sling failure.

Anesthetic considerations for a novel anterior surgical approach to pediatric scoliosis correction.

BACKGROUND: Idiopathic scoliosis is a condition that may require surgical correction. Limitations of previous surgical modalities, however, created the need for novel methods of repair. One such technique, a newer form of anterolateral scoliosis correction, has shown considerable promise, which our center has had substantial experience performing. AIM: In this article, we present the case details of our first 105 patients for the purposes of describing the evolution and details of the anesthetic management and considerations for this procedure. METHODS: A retrospective review of medical records for 105 patients undergoing anterolateral instrumentation procedure for idiopathic scoliosis correction done at a single institution from May 2014 to June 2016 was performed. The details of perioperative management as well as surgical technique were reported for all patients. RESULTS: The mean age for patients was 14.8 years (range 10-18); the mean weight was 49.9 kg (range 25-82). Unilateral procedures were performed on 46.7%, with bilateral and hybrid procedures performed on 50.5% and 4.7%, respectively. The median number of levels corrected was 8 (interquartile range [IQR] 7-9) for unilateral, right 7 (IQR 6-7) and left 5 (IQR 4-5) for bilateral, and 4 (IQR 4-4.5) for hybrids. The average estimated blood loss (EBL) was 310 mL±138, with cell salvaged blood transfused in 61% of patients, and allogenic blood transfusion required in only two patients. CONCLUSIONS: The described anesthetic and analgesic management provides a framework for delivering perioperative care for this challenging procedure, which is gaining popularity as a modality for scoliosis correction.

Variables affecting maximum urethral closure pressure (MUCP) and abdominal leak point pressure (ALPP) measurements.

INTRODUCTION AND HYPOTHESIS: The relationship between pelvic floor muscles and measurements of urethral function is not well studied. It is not known whether adjusting for clinical, demographic and urodynamic parameters would improve the association between MUCP and ALPP. Our hypothesis was that pelvic floor muscle strength (PFMS) influences the relationship between MUCP and ALPP. METHODS: This was a retrospective study of women who underwent a complex urodynamic study with evaluation of MUCP and ALPP using ICD-9 codes with documentation of PFMS. RESULTS: Urodynamic stress incontinence was confirmed in 478 patients, of whom 323 had MUCP recorded and 263 had both MUCP and ALPP recorded. Women with higher PFMS had a higher MUCP. In regression analysis ALPP at 150 mL and MUCP were weakly associated (coefficient 0.43, 95% CI 0.08-0.78; p = 0.02), whereas ALPP at capacity and MUCP were moderately associated (coefficient 0.60, 95% CI 0.25-0.95; p < 0.001). CONCLUSIONS: This study showed that MUCP and ALPP at 150 mL were weakly associated and that this improved to a moderate association for ALPP at capacity. MUCP increased with increasing PFMS among women with stress urinary incontinence and decreased with increasing age. There was no evidence that ALPP was associated with PFMS or age. The relationship between MUCP and ALPP was unchanged when accounting for covariates of PFMS (age, parity, BMI, prior procedure, urethral mobility, bladder capacity, stage of cystocele, or stage of uterine or apical prolapse).

Symptomatic Epidermoid Cyst Presenting as a Paravaginal Mass.

BACKGROUND: Ischioanal fossa epidermoid cysts are uncommon masses of epithelial origin and are believed to be either congenital or the result of trauma. Surgical excision is preferred as opposed to incision and drainage because these masses may enlarge, recur, become infected, or undergo malignant transformation. CASE: This report describes a case of a 62-year-old woman who presented for evaluation of vaginal and perineal discomfort and fullness. Physical examination and computed tomography scan revealed a 7.1-cm cystic mass in the left ischioanal space. Transgluteal surgical excision was performed and pathology revealed an epidermoid cyst. The patient recovered with symptomatic improvement. CONCLUSIONS: This report demonstrates a rare case of ischioanal fossa epidermoid cyst. In cases of rectal masses, cystic lesions should be considered. Thorough physical examination, imaging studies, and proper surgical management of these masses can improve patient symptomatology, prevent recurrence, and also decrease the risk of malignant transformation.

Utility of antimüllerian hormone level obtained for infertility assessment for alerting to ovarian tumor.

BACKGROUND: Antimüllerian hormone is a marker of ovarian reserve and is now routinely measured in women seeking infertility treatment. CASE: A 42-year-old woman, gravida 1, abortus 1, presented with secondary infertility. Obtained originally for assessment of ovarian reserve, an antimüllerian hormone of more than 160 ng/mL raised suspicion for a granulosa cell tumor. A laparoscopic right salpingo-oophorectomy, pelvic washings, dilation and curettage, and peritoneal and omental biopsies were performed. A well-differentiated granulosa cell tumor confined to the right ovary was consistent with stage 1A disease. CONCLUSION: As the use of antimüllerian hormone becomes more common for ovarian reserve testing, providers need to maintain an awareness for neoplastic disease with abnormal values.

Fluoroscopic organ and tissue-specific radiation exposure by sex and body mass index during ureteroscopy.

INTRODUCTION: Although radiation exposure from CT and plain film imaging has been characterized, the radiation received by patients during modern-era fluoroscopy has not been well described. The purposes of this study were to measure absolute organ and tissue-specific radiation doses during ureteroscopy and to determine the influence of body mass index (BMI) and sex on these doses. MATERIALS AND METHODS: Eight cadavers underwent a simulated left ureteroscopy. Using a modern C-arm with automatic exposure control settings, thermoluminescent dosimeters were exposed for a fluoroscopy time of 145 seconds (mean time of clinical ureteroscopies from 2006 to 2008). Total tissue exposures were compared by BMI and between sexes using the Wilcoxon signed ranks test and the Mann-Whitney test with p < 0.05 considered significant. RESULTS: Among all cadavers, radiation doses were significantly lower in all contralateral organs excluding the gonad (p < 0.012). Doses were similar bilaterally in the gonad in cadavers with BMI <30, and in all organs in cadavers with BMI >30 (p > 0.05). There were significantly higher mean bilateral gonadal doses in female cadavers (3.4 mGy left and 1.9 mGy right) compared with male cadavers (0.36 mGy left and 0.39 mGy right). The highest cancer risk increase was seen at the posterior skin equivalent to 104 additional cancers per 100,000 patients. CONCLUSION: Contralateral doses were lower for all organs except the gonad when the BMI was <30. In contrast, when the BMI was >30, there was no difference in radiation dose delivered to the ipsilateral and contralateral organs. Gonadal doses were significantly higher in female cadavers. Modern-era fluoroscopy remains a significant source of radiation exposure and steps should be taken to minimize exposure during ureteroscopy.

Multidetector computed tomographic characteristics of nonabsorbable polymer versus titanium ligature clips in a vascular model.

OBJECTIVE: Multidetector cardiac computed tomography is commonly performed to evaluate coronary bypass grafts, but titanium clips result in significant image artifact. Multidetector cardiac computed tomographic characteristics of newly developed nonabsorbable polymer clips are unknown. This study was undertaken to compare the image characteristics of polymer clips and titanium clips applied to a vascular model. METHODS: A vascular model was created with two porcine internal thoracic arteries. Branches were ligated with 5 titanium clips on one vessel and 6 polymer clips on the other. Vessels were imaged under pressure with normal saline solution in a 16-detector computed tomographic scanner. Image intensity was quantified in absolute Hounsfield units for clips and adjacent lumen and then normalized to the average lumen intensity. RESULTS: No difference in absolute intensity was found between polymer clips and adjacent lumen (polymer clip 1021.2 +/- 19.0 absolute Hounsfield units, adjacent lumen 1001.7 +/- 15.7 absolute Hounsfield units, P = .095). A statistically significant difference was noted between titanium clips and adjacent lumen (titanium clips 3408.8 +/- 177.3 absolute Hounsfield units, adjacent lumen 1072.7 +/- 52.1 absolute Hounsfield units, P < .0001). A statistically significant difference was also noted between titanium and polymer clips (P < .0001). CONCLUSION: The use of polymer clips in coronary bypass grafts should result in significantly improved multidetector cardiac computed tomographic image quality.

Carbonic anhydrase inhibitors: inhibition of the human isozymes I, II, VA, and IX with a library of substituted difluoromethanesulfonamides.

An inhibition study of the human cytosolic isozymes I, and II, the mitochondrial isoform VA, and the tumor-associated, transmembrane isozyme IX of carbonic anhydrase (CA, EC 4.2.1.1) with a library of aromatic/heteroaromatic/polycyclic difluoromethanesulfonamides is reported. Most of the inhibitors were derivatives of benzenedifluoromethanesulfonamide incorporating substituted-phenyl moieties, or were methylsulfonamide and difluoromethyl-sulfonamide derivatives of the sulfamates COUMATE and EMATE, respectively. Except for the methylsulfonamide-COUMATE derivative which behaved as a potent CA II inhibitor (K(I) of 32nM), these sulfonamides were moderate inhibitors of all isozymes, with inhibition constants in the range of 96-5200nM against hCA I, of 80-670nM against hCA II, and of 195-9280nM against hCA IX, respectively. Remarkably, some derivatives, such as 3-bromophenyl-difluoromethanesulfonamide, showed a trend to selectively inhibit the mitochondrial isoform CA VA, showing selectivity ratios for inhibiting CA VA over CA II of 3.53; over CA I of 6.84 and over CA IX of 9.34, respectively, although it is a moderate inhibitor (K(I) of 160nM). Some of these derivatives may be considered as leads for the design of isozyme selective CA inhibitors targeting the mitochondrial isozyme CA VA, with potential use as anti-obesity agents.

Synthesis of a non-hydrolyzable estrone sulfate analogue bearing the difluoromethanesulfonamide group and its evaluation as a steroid sulfatase inhibitor.

Steroid sulfatase (STS) catalyzes the hydrolyis of steroidal sulfates such as estrone sulfate (ES1) and is considered to be an attractive target in the treatment of steroid dependent cancers. A non-hydrolyzable estrone sulfate (ES1) analogue bearing an alpha,alpha-difluorosulfonamide moiety at the 3-position on the A-ring, compound , was synthesized. Key to the success of this synthesis was the first use of the allyl group as a sulfonamide protecting group. The pK(a) of this ES1 mimic in 0.1 M bis-tris propane, 10% DMSO was determined to be 8.05 using 19F NMR. Compound is a reversible inhibitor with a K(i) similar to that of its sulfonate analogue at pH 7.0. It is more potent than its non-fluorinated sulfonamide analogue and, its inhibitory potency increases with increasing pH, a trend opposite to that of other STS inhibitors. Possible reasons for this are presented.