Association of Surgical Approaches and Outcomes in Total Mesorectal Excision and Margin Status for Rectal Cancer.

INTRODUCTION: Despite being a key metric with a significant correlation with the outcomes of patients with rectal cancer, the optimal surgical approach for total mesorectal excision (TME) has not yet been identified. The aim of this study was to assess the association of the surgical approach on the quality of TME and surgical margins and to characterize the surgical and long-term oncologic outcomes in patients undergoing robotic, laparoscopic, and open TME for rectal cancer. METHODS: Patients with primary, nonmetastatic rectal adenocarcinoma who underwent either lower anterior resection or abdominoperineal resection via robotic (Rob), laparoscopic (Lap), or open approaches were selected from the US Rectal Cancer Consortium database (2007-2017). Quasi-Poisson regression analysis with backward selection was used to investigate the relationship between the surgical approach and outcomes of interest. RESULTS: Among the 664 patients included in the study, the distribution of surgical approaches was as follows: 351 (52.9%) underwent TME via the open approach, 159 (23.9%) via the robotic approach, and 154 (23.2%) via the laparoscopic approach. There were no significant differences in baseline demographics among the three cohorts. The laparoscopic cohort had fewer patients with low rectal cancer (<6 cm from the anal verge) than the robotic and open cohorts (Lap 28.6% versus Rob 59.1% versus Open 45.6%, P = 0.015). Patients who underwent Rob and Lap TME had lower intraoperative blood loss compared with the Open approach (Rob 200 mL [Q1, Q3: 100.0, 300.0] versus Lap 150 mL [Q1, Q3: 75.0, 250.0] versus Open 300 mL [Q1, Q3: 150.0, 600.0], P < 0.001). There was no difference in the operative time (Rob 243 min [Q1, Q3: 203.8, 300.2] versus Lap 241 min [Q1, Q3: 186, 336] versus Open 226 min [Q1, Q3: 178, 315.8], P = 0.309) between the three approaches. Postoperative length of stay was shorter with robotic and laparoscopic approach compared to open approach (Rob 5.0 d [Q1, Q3: 4, 8.2] versus Lap 5 d [Q1, Q3: 4, 8] versus Open 7.0 d [Q1, Q3: 5, 9], P < 0.001). There was no statistically significant difference in the quality of TME between the robotic, laparoscopic, and open approaches (79.2%, 64.9%, and 64.7%, respectively; P = 0.46). The margin positivity rate, a composite of circumferential margin and distal margin, was higher with the robotic and open approaches than with the laparoscopic approach (Rob 8.2% versus Open 6.6% versus Lap 1.9%, P = 0.17), Rob versus Lap (odds ratio 0.21; 95% confidence interval 0.05, 0.83) and Rob versus Open (odds ratio 0.5; 95% confidence interval 0.22, 1.12). There was no difference in long-term survival, including overall survival and recurrence-free survival, between patients who underwent robotic, laparoscopic, or open TME (Figure 1). CONCLUSIONS: In patients undergoing surgery with curative intent for rectal cancer, we did not observe a difference in the quality of TME between the robotic, laparoscopic, or open approaches. Robotic and open TME compared to laparoscopic TME were associated with higher margin positivity rates in our study. This was likely due to the higher percentage of low rectal cancers in the robotic and open cohorts. We also reported no significant differences in overall survival and recurrence-free survival between the aforementioned surgical techniques.

Achieving optimal balance: tuning electrical and optical characteristics of carbon electrodes for emerging photovoltaics.

Transparent and conductive electrodes (TCEs) are essential for various optoelectronic and photovoltaic applications, but they often require expensive and complex fabrication methods. In this paper, a unique low-cost, eco-friendly, and scalable method of fabricating TCEs using spray-coated carbon ink is investigated. Firstly the carbon particles used for this process underwent a size reduction from 20 microns to 0.96 microns via ball milling. Then ink was prepared by mixing graphite powder (for conductivity), ethyl cellulose (for viscosity), and toluene (for solubility) with different weight-per-volume ratios (w/v) of 5%, 10%, and 15%. The TCEs were fabricated by spray coating the ink onto glass substrates using an airbrush. The sheet resistance (Ω sq-1) and transparency (%) of the TCEs were measured by a digital multimeter (DMM) probe method and a UV-vis spectrophotometer, respectively. The sheet resistance of the TCEs decreased linearly from 60 to 20 Ω sq-1, while the transparency decreased exponentially from 37.18% to 18.88% as the ink concentration increased from 5% to 15% w/v. This paper also reports the reflectance and absorbance values for each ink concentration. The results demonstrate that spray-coated carbon ink TCEs achieve sheet resistance and transparency values of 20 Ω sq-1 and 18.88%, respectively, with low-cost and eco-friendly materials and methods, which are desirable for optoelectronic and photovoltaic applications. These TCEs can play an important role as electrodes in semi-transparent perovskite cells enhancing their stability and overall efficiency.

Beyond bias: A registered examination of the validity of using line bisection to measure non-lateralised attention.

Line bisection is a task widely used to assess lateral asymmetries of attention, in which participants are asked to mark the midpoint of a horizontal line. The directional bisection error (DBE) from the objective midpoint of the line is the traditional measure of performance. However, an alternative method of studying the bisection behaviour, the endpoint weightings method, has been proposed. This method produces two measures of performance: endpoint weightings bias (EWB) and endpoint weightings sum (EWS). While EWB measures attentional asymmetry, it has been suggested that EWS quantifies the total (non-lateralised) attention allocated to the task. If EWS provides a valid index of non-lateralised attention, then changes in tonic and phasic arousal should systematically affect EWS. In this article, we formally tested this prediction, using time on task to manipulate tonic arousal and unpredictable auditory tones, presented simultaneously with line stimuli, to manipulate phasic arousal. Our registered analyses revealed that neither of our manipulations for tonic or phasic arousal significantly influenced EWS. Therefore, the null hypotheses cannot be rejected. An exploratory analysis of all trials and conditions revealed a significant reduction in EWS with time spent on task. However, the lack of any significant effect of the alerting tone on EWS suggests that EWS may not be a valid measure of generalised attention to the task.

Impact of neoadjuvant immunotherapy on postoperative complications after surgery for rectal cancer.

INTRODUCTION: Despite the increasing use of immunotherapy in treating various cancer types, there is still limited understanding of its impact on surgical complications. We used a national database to examine the difference in surgical outcomes for rectal cancer patients who received standard neoadjuvant chemoradiation plus neoadjuvant immunotherapy and patients who received neoadjuvant chemoradiation only. METHODS: This retrospective cohort study used the National Cancer Database (NCDB). We selected patients aged 18-90 with T1-3, N1-2, and M0 rectal cancer who underwent curative-intent surgery between 2010 and 2020. We performed a 1:1 propensity match to control for patient age, sex, Charlson-Deyo comorbidity index, surgical approach, and tumor site. Our primary outcome was difference in surgical outcomes (hospital length of stay, unplanned 30-day readmission, 30-day mortality) between the two groups. Secondary outcomes included days from diagnosis to surgery and pathologic outcomes. RESULTS: Our study included 26 229 patients, of which 126 received immunotherapy in addition to chemoradiation and 26 103 received only chemoradiation. In our matched population of 125 pairs of patients, patients who received immunotherapy and chemoradiation underwent surgery later compared to patients who only received chemoradiation (median 245 vs. 144 days, p < 0.001). There were no significant differences in median length of stay (5 vs. 5 days, p = 0.202), unplanned 30-day readmission (7 vs. 9, p = 0.617), and 30-day mortality (0 vs. 1, p = 1.000) between the two groups. CONCLUSION: Neoadjuvant immunotherapy for rectal cancer is not associated with adverse surgical outcomes. This work can help clinicians optimize treatment protocols and move closer toward strategies tailored to specific patient profiles.

To Resect or Not to Resect: A Nationwide Comparison of Management of Sigmoid Volvulus.

INTRODUCTION: Despite the high recurrence rate of sigmoid volvulus, there is reluctance to perform a prophylactic colectomy in frail patients due to the operation's perceived risks. We used a nationally representative database to compare risk of recurrence in patients undergoing a prophylactic colectomy versus endoscopic detorsion alone. METHODS: We performed a retrospective cohort study using the National Readmission Database (2016-2019) including patients aged ≥18 y who had an emergent admission for sigmoid volvulus and underwent endoscopic detorsion on the day of admission. We performed a 1:1 propensity matching adjusting for patient demographics, frailty score comprising of 109 components, and hospital characteristics. Our primary outcome was readmission due to colonic volvulus and secondary outcomes included mortality, complications, length of stay (LOS), and costs during index admission and readmission. We performed a subgroup analysis in patients with Hospital Frailty Score >5. RESULTS: We included 2113 patients of which 1046 patients (49.5%) underwent a colectomy during the initial admission. In the matched population of 830 pairs, readmission due to colonic volvulus was significantly lower in patients undergoing endoscopy followed by colectomy than endoscopy alone. Patients undergoing a colectomy had higher gastric and renal complications, longer LOS, and higher costs but no difference in mortality. In the subgroup analysis of frail patients, readmission was significantly lower in patients with prophylactic colectomy with no significant difference in mortality in 439 matched patients. CONCLUSIONS: Prophylactic colectomy was associated with lower readmission, a higher rate of complications, increased LOS, and higher costs compared to sigmoid decompression alone.

Development of a Predictive Nomogram for Circumferential Resection Margin in Rectal Cancer Surgery.

INTRODUCTION: Circumferential resection margin (CRM) is a key quality metric and predictor of oncologic outcomes and overall survival following surgery for rectal cancer. We aimed to develop a nomogram to identify patients at risk for a positive CRM in the preoperative setting. METHODS: We performed a retrospective evaluation of the National Cancer Database from 2010 to 2014 for patients with clinical stage I-III rectal cancer who underwent total mesorectal excision. Patients were excluded for emergency operation, resection for cancer recurrence, palliative resection, transanal resection, and missing CRM status. The primary outcome was positive CRM. Secondary outcomes included overall survival. RESULTS: There were 28,790 patients included. 2245 (7.8%) had a positive CRM. Higher tumor grade, lack of neoadjuvant chemotherapy, mucinous/signet tumor histology, open approach, abdominoperineal resection, higher T stage, lymphovascular invasion, and perineural invasion were all significantly associated with positive CRM (P < 0.05) and were included in the nomogram. The C-statistic was 0.703, suggesting a good predictive model. CONCLUSIONS: Positive CRM is associated with specific patient demographics and tumor characteristics. These factors can be used along with preoperative MRI to predict CRM positivity in the preoperative period and plan accordingly.

Association of omental pedicled flap with anastomotic leak following low anterior resection for rectal cancer.

BACKGROUND AND OBJECTIVES: Anastomotic leak following colorectal anastomosis adversely impacts short-term, oncologic, and quality-of-life outcomes. This study aimed to assess the impact of omental pedicled flap (OPF) on anastomotic leak among patients undergoing low anastomotic resection (LAR) for rectal cancer using a multi-institutional database. METHODS: Adult rectal cancer patients in the US Rectal Cancer Consortium, who underwent a LAR for stage I-III rectal cancer with or without an OPF were included. Patients with missing data for surgery type and OPF use were excluded from the analysis. The primary outcome was the development of anastomotic leaks. Multivariable logistic regression was used to determine the association. RESULTS: A total of 853 patients met the inclusion criteria and OPF was used in 106 (12.4%) patients. There was no difference in age, sex, or tumor stage of patients who underwent OPF versus those who did not. OPF use was not associated with an anastomotic leak (p = 0.82), or operative blood loss (p = 0.54) but was associated with an increase in the operative duration [ß = 21.42 (95% confidence interval = 1.16, 41.67) p = 0.04]. CONCLUSIONS: Among patients undergoing LAR for rectal cancer, OPF use was associated with an increase in operative duration without any impact on the rate of anastomotic leak.

Colon and Rectal Surgery Fellowship Applicant and Matching Trends in the United States: An Analysis of National Resident Matching Program Data.

BACKGROUND: Colon and Rectal Surgery fellowships are training programs that aim to train surgeons in the management of small bowel, colon, rectal, and anal pathologies. OBJECTIVE: We investigated trends in Colon and Rectal Surgery fellowship match to help applicants anticipate future fellowship application cycles. DESIGN: This was a retrospective cohort study of applicants in the Colon and Rectal Surgery match from 2009 to 2023. Proportion of positions filled, match rates, and rank-order lists were collected. The impact of US-MD, non-US-MD, and DO status on match rate was assessed. We used the Mann Kendall trend test to obtain tau statistic and P-value for temporal trends over time, while associations between categorical variables were investigated by a chi-square test. RESULTS: Fellowship programs increased from 43 to 67, positions increased from 78 to 110, and number of applicants rose from 113 to 135. Nearly all positions were filled from 2009 to 2023 (range: 96.3%-100%). The overall match rate fluctuated between 67.3% and 80.7%. The match rate over the past 5 years was 72.0%. The match rate for US-MDs was 80.0%, while non-US-MDs had a 56.2% match rate. The percentage matching at each rank were first choice 28.0%, second choice 10.4%, third choice 6.9%, and fourth choice or lower 23.5%. CONCLUSION: Despite an increase in Colon and Rectal Surgery fellowship positions, the overall match rate has not changed significantly over the years, mainly as a result of increased applicants.

Impact of trans-anal versus laparoscopic total mesorectal excision on the surgical and pathologic outcomes of patients with rectal cancer: meta-analysis of randomized controlled trials.

BACKGROUND: Despite its profound impact on the oncologic outcomes of rectal cancer, the most optimal surgical approach to total mesorectal excision (TME) has not been identified yet. All previous meta-analyses on this subject have been based on observational studies. This meta-analysis was conducted to assess the surgical and oncologic outcomes of laparoscopic TME (LaTME) compared to trans-anal TME (TaTME), utilizing only randomized controlled trials. DESIGN: Systematic review and meta-analysis of randomized controlled trials. METHODS: We searched electronic databases (MEDLINE, Cochrane CENTRAL, Clinicaltials.gov) from 2010 onwards, for all published clinical trials comparing TaTME to LaTME. Results are presented as risk ratios, with 95% CI, and pooled using the random effects model. RESULTS: A total of 1691 patients, from 6 eligible randomized controlled trials, were included for analysis. Analyzed data showed no significant difference in morbidity (RR: 0.85, p = 0.15), mortality (RR: 0.50, p = 0.44), conversion to open (RR: 0.40, p = 0.07), or anastomotic leakage (RR: 0.73, p = 0.10) between TaTME and LaTME. There was also no difference in the rate of positive distal resection margin (DRM) (RR: 0.55, p = 0.10) or positive circumferential resection margin (CRM) (RR: 0.67, p = 0.30). Patients undergoing TaTME were more likely to have a complete TME (RR: 1.06, p = 0.002) and shorter hospital stays (RR: - 0.97, p < 0.00001). CONCLUSIONS: Patients undergoing TaTME for rectal cancer were more likely to have a complete TME when compared to LaTME, though this did not translate into improved distal or circumferential resection margin. Additionally, TaTME and LaTME had similar surgical outcomes except for shorter length of stay with TaTME.

Permanganate activation with Mn oxides at different oxidation states: Insight into the surface-promoted electron transfer mechanism.

The development of new strategies to improve the removal of organic pollutants with permanganate (KMnO4) is a hot topic in water treatment. While Mn oxides have been extensively used in Advanced Oxidation Processes through an electron transfer mechanism, the field of KMnO4 activation remains relatively unexplored. Interestingly, this study has discovered that Mn oxides with high oxidation states including γ-MnOOH, α-Mn2O3 and α-MnO2, exhibited excellent performance to degrade phenols and antibiotics in the presence of KMnO4. The MnO4- species initially formed stable complexes with the surface Mn(III/IV) species and showed an increased oxidation potential and electron transfer reactivity, caused by the electron-withdrawing capacity of the Mn species acting as Lewis acids. Conversely, for MnO and γ-Mn3O4 with Mn(II) species, they reacted with KMnO4 to produce cMnO2 with very low activity for phenol degradation. The direct electron transfer mechanism in α-MnO2/KMnO4 system was further confirmed through the inhibiting effect of acetonitrile and the galvanic oxidation process. Moreover, the adaptability and reusability of α-MnO2 in complicated waters indicated its potential for application in water treatment. Overall, the findings shed light on the development of Mn-based catalysts for organic pollutants degradation via KMnO4 activation and understanding of the surface-promoted mechanism.

Polyarteritis nodosa: a case report of isolated large bowel involvement and surgical intervention.

Polyarteritis nodosa (PAN) is a necrotizing vasculitis commonly affecting small-sized vessels and medium-sized vessels. We present the case of surgical resection for ischemic colitis secondary to PAN. A 26-year-old woman presented with left lower quadrant pain, diarrhea and bloody stools. Colonoscopy showed diffuse circumferential ulceration and necrotic lining from the sigmoid colon to the splenic flexure. A subsequent computed tomography angiography (CTA) revealed left colonic wall thickening, hypoenhancement and multiple inferior mesenteric artery aneurysms, concerning for vasculitis. Ensuing laboratory workup all returned negative. Worsening pain, left-sided peritonitis, tachycardia and rising white blood cell necessitated a colectomy from the proximal descending to upper rectum with an end colostomy. Surgical pathology showed features consistent with PAN. The patient improved significantly after surgery and was discharged on a steroid taper and later started on mycophenolate mofetil. This case is a unique presentation of isolated large intestinal involvement and was treated with both medical and surgical interventions.

Association of hospital volume with conversion to open from minimally invasive colectomy in patients with diverticulitis: A national analysis.

BACKGROUND: Despite the known advantages of minimally invasive surgery (MIS) for diverticular disease, the impact of conversions to open (CtO) colectomy remains understudied. The present study used a nationally representative database to characterize risk factors and outcomes associated with CtO in patients with diverticular disease. METHODS: All elective adult hospitalizations entailing colectomy for diverticulitis were identified in the 2017-2019 Nationwide Readmissions Database. Annual institutional caseloads of MIS and open colectomy were independently tabulated. Restricted cubic splines were utilized to non-linearly estimate the risk-adjusted association between hospital volumes and CtO. Additional regression models were developed to evaluate the association of CtO with outcomes of interest. RESULTS: Of an estimated 110,281 patients with diverticulitis who met study criteria, 39.3% underwent planned open colectomy, 53.3% completed MIS, and 7.4% had a CtO. Following adjustment, an inverse relationship between hospital MIS volume and risk of CtO was observed. In contrast, increasing hospital open volume was positively associated with greater risk of CtO. On multivariable analysis, CtO was associated with lower odds of mortality (AOR 0.3, p = 0.001) when compared to open approach, and similar risk of mortality when compared to completed MIS (AOR 0.7, p = 0.436). CONCLUSION: In the present study, institutional MIS volume exhibited inverse correlation with adjusted rates of CtO, independent of open colectomy volume. CtO was associated with decreased rates of mortality compared to planned open approach but equivalence risk relative to completed MIS. Our findings highlight the importance of MIS experience and suggest that MIS may be safely pursued as the initial surgical approach among diverticulitis patients.

The use of surgical intervention for lower gastrointestinal bleeding and its association with clinical outcomes and resource use.

BACKGROUND: To assess the use of surgical intervention for lower gastrointestinal bleeding and evaluate its associated factors. METHODS: The 2016 to 2019 National Inpatient Sample was queried to identify non-elective adult (≥18 years) hospitalizations for lower gastrointestinal bleeding. The International Classification of Diseases, 10th Revision, codes were used to ascertain patient characteristics, including signs of hemodynamic instability, potential lower gastrointestinal bleed source, and transfusion of blood products, as well as endoscopic, radiologic, and surgical intervention. Multivariable regression analyses were used to elucidate factors associated with operative management of lower gastrointestinal bleeding and evaluate its associated mortality, length of stay, and hospitalization costs. RESULTS: Of an estimated 364,495 patients, 1.7% underwent an operation for lower gastrointestinal bleeding. Compared to those managed conservatively, patients who underwent surgical intervention more commonly had diverticular-related bleeding, signs of hypovolemia, and less frequently underwent endoscopic intervention. After the adjustment of patient and hospital characteristics, ischemic colitis (adjusted odds ratio 7.5, 95% confidence interval 1.8-30.9, ref: hemorrhoids), hemodynamic instability (adjusted odds ratio 1.7, 95% confidence interval 1.5-2.0), and angiographic embolization (adjusted odds ratio 4.9, 95% confidence interval 3.9-6.0, ref: no endoscopic/radiologic intervention) were associated with greater odds of surgical intervention. Additionally, surgical intervention portended greater odds of in-hospital mortality (adjusted odds ratio 6.2, 95% confidence interval 4.5-8.5), a longer length of stay (8.5 days, 95% confidence interval 8.0-9.0), and greater hospitalization cost ($29.1K, 95% confidence interval 26.7K-31.5K). CONCLUSION: Operative management of lower gastrointestinal bleeding is rare and associated with significant morbidity and mortality compared to those managed conservatively. However, when surgical intervention is indicated, preoperative patient characteristics should be used to identify those at greater risk of an operation to facilitate early surgical consultation and inform expectations during the perioperative period.

A Rare Case of Neural Epidermal Growth Factor-Like 1 Protein (NELL-1) Antigen-Associated Membranous Nephropathy.

Membranous nephropathy (MN) is an autoimmune disease resulting in nephrotic syndrome. Neural epidermal growth factor-like 1 protein (NELL-1) has been shown to cause a rare form of MN that is more likely to be associated with malignancy. We present a case of a 73-year-old female who was found to have a NELL-1-associated segmental MN. She presented complaining of generalized weakness, chills, and poor appetite, worsening over a one-week duration. Her kidney functions were noted to be markedly deranged, with a computed tomography scan of the abdomen showing evidence of chronic kidney disease. Further testing confirmed heavy proteinuria, although the etiology was still uncertain. A kidney biopsy revealed granular subepithelial immunoglobulin G deposits with subsequent immunohistochemical staining for NELL-1 antigen being positive. She improved with supportive care over the next few days. Despite an extensive workup, no underlying malignancy was found. NELL-1 is a rare yet recognized antigen target for the development of MN. Up to a third of patients with NELL-1-associated MN have associated cancer, thus requiring evaluation for underlying malignancy in this cohort.

Agranulocytosis Secondary to Cancer Chemotherapy Associated With Higher In-Hospital Mortality in Patients With Central Line Insertion During a Hospital Stay.

Background Agranulocytosis secondary to cancer chemotherapy (ASCC) remains a leading cause of morbidity and mortality. Central line-associated bloodstream infections (CLABSI) are also particularly prevalent in these populations and may portend a poorer outcome. Our study serves to investigate the relationship between patients with agranulocytosis secondary to cancer chemotherapy and the insertion of a central venous catheter (CVC) with respect to in-hospital mortality. Methods and results We utilized the National Inpatient Survey 2019 database. We utilized the International Classification of Diseases (ICD)-10 CM codes to identify ASCC and other medical comorbidities. We utilized ICD-10 PCS codes to identify CVC insertions. Multivariate logistic regression was utilized to study the effect of CVC insertion on in-hospital mortality. In patients with ASCC, CVC insertion was associated with a higher in-hospital mortality (unadjusted: 11.9% vs. 1%, p<0.001, adjusted OR 19.27, 95% CI 5.84 - 65.6, p<0.001) adjusted for baseline characteristics and other comorbidities. Patients in the study cohort who were older than 70 years of age also had a higher in-hospital mortality relative to younger age groups (adjusted OR 2.31, 95% CI 1.04-5.13, p<0.039). Conclusion In patients with ASCC, CVC insertion during hospitalization is associated with higher in-hospital mortality.

BK-Virus-Induced Hemorrhagic Cystitis in a Patient With Graft-Versus-Host Disease.

The BK virus is a polyomavirus known to particularly affect transplant recipients. An important complication caused by BK virus infection in bone marrow transplant patients is hemorrhagic cystitis. We present a 31-year-old male with a history of bone marrow transplantation complicated by graft-versus-host disease (GVHD) and was diagnosed with BK virus-related hemorrhagic cystitis. He presented with gross hematuria and suprapubic and penile pain for one week. He has a significant past medical history of acute B-cell lymphocytic leukemia for which he has successfully undergone allogenic bone marrow transplantation, which was complicated by GVHD. Imaging revealed significant bladder wall thickening which prompted an evaluation for BK virus-induced hemorrhagic cystitis. A urinary specimen was sent for BK virus polymerase chain reaction (PCR) which was strongly positive, confirming the infection. He was managed supportively throughout his hospitalization and improved with symptomatic management alone. Our case demonstrates one of the main complications caused by the BK virus in allogeneic bone marrow transplant patients in the setting of GVHD and is an important differential to keep in mind when treating patients presenting with hematuria after bone marrow transplantation.

An Aggressive Case of Adrenocortical Carcinoma Complicated by Paraneoplastic Cushing's Syndrome.

Adrenocortical carcinoma (ACC) is a rare endocrine malignancy with a poor prognosis. Surgical resection may be curative if localized disease is identified, although recurrence is common. Research shows that the use of adjuvant therapeutic regimens such as EDP-M (combination of mitotane, etoposide, doxorubicin, and cisplatin) in high-risk patients has survival benefits. A 75-year-old female was incidentally found to have a right adrenal heterogeneous internal enhancement measuring 5.0 x 3.7cm. The workup confirmed autonomous adrenal production of corticosteroids and she was referred to surgery for an adrenalectomy. A T2 ACC with positive margins and lympho-vascular invasion was resected, following which she was started on external beam radiation followed by four cycles of carboplatin and etoposide. Despite initial treatments, she was diagnosed with refractory metastatic disease at subsequent follow-ups. Pembrolizumab immunotherapy was started, but disease progression continued, and she was eventually transitioned to mitotane 1g twice daily. She continued to worsen and was eventually transitioned to hospice care. The management of ACC remains diagnostically challenging, especially because most patients do not present until an advanced stage of disease. Surgery is commonly employed with a curative intent, and opinions regarding adjuvant cytotoxic therapy and/or radiotherapy remain mixed.

Systematic, comprehensive, evidence-based approach to identify neuroprotective interventions for motor neuron disease: using systematic reviews to inform expert consensus.

OBJECTIVES: Motor neuron disease (MND) is an incurable progressive neurodegenerative disease with limited treatment options. There is a pressing need for innovation in identifying therapies to take to clinical trial. Here, we detail a systematic and structured evidence-based approach to inform consensus decision making to select the first two drugs for evaluation in Motor Neuron Disease-Systematic Multi-arm Adaptive Randomised Trial (MND-SMART: NCT04302870), an adaptive platform trial. We aim to identify and prioritise candidate drugs which have the best available evidence for efficacy, acceptable safety profiles and are feasible for evaluation within the trial protocol. METHODS: We conducted a two-stage systematic review to identify potential neuroprotective interventions. First, we reviewed clinical studies in MND, Alzheimer's disease, Huntington's disease, Parkinson's disease and multiple sclerosis, identifying drugs described in at least one MND publication or publications in two or more other diseases. We scored and ranked drugs using a metric evaluating safety, efficacy, study size and study quality. In stage two, we reviewed efficacy of drugs in MND animal models, multicellular eukaryotic models and human induced pluripotent stem cell (iPSC) studies. An expert panel reviewed candidate drugs over two shortlisting rounds and a final selection round, considering the systematic review findings, late breaking evidence, mechanistic plausibility, safety, tolerability and feasibility of evaluation in MND-SMART. RESULTS: From the clinical review, we identified 595 interventions. 66 drugs met our drug/disease logic. Of these, 22 drugs with supportive clinical and preclinical evidence were shortlisted at round 1. Seven drugs proceeded to round 2. The panel reached a consensus to evaluate memantine and trazodone as the first two arms of MND-SMART. DISCUSSION: For future drug selection, we will incorporate automation tools, text-mining and machine learning techniques to the systematic reviews and consider data generated from other domains, including high-throughput phenotypic screening of human iPSCs.

Association of Anemia with Parathyroid Hormone Levels and Other Factors in Patients with End-Stage Renal Disease Undergoing Hemodialysis: A Cross-Sectional, Real-World Data Study in Pakistan.

End-stage renal disease (ESRD) patients are mostly managed with maintenance hemodialysis (MHD). ESRD patients on MHD also present with many complications, such as anemia, hyperparathyroidism, and hepatitis prevalence. This study depicts the real-world scenario of anemia among MHD and end-stage renal disease patients in the Pakistani population. A retrospective, multicentric, and real-world data analytical study was conducted at 4 dialysis centers in Pakistan. The study had a sample size of n = 342 patients on maintenance hemodialysis. The data were gathered from the medical records of patients. Data analysis was performed using STATA Version 16. Statistical significance was gauged at a 0.05 level of significance. According to our results, the mean age of the patients was 45 (±15) years. Most of the patients were male (n = 234, 68.4%), whereas 58.1% of the patients were maintained on twice-weekly hemodialysis. The most commonly reported comorbidities were hypertension and diabetes mellitus. The frequency of dialysis (P < 0.01) and comorbidities (P = 0.009) had a significant association with anemia in MHD patients. The majority of the patients had hyperparathyroidism (52%) with anemia. Upon performing binary logistic regression, multivariate analysis displayed a similar odds value for having anemia in patients with every additional month in the duration of hemodialysis (OR 1.01, P = 0.001), the odds of anemic patients having a positive antihepatitis-C antibody (OR 2.22, P = 0.013), and the odds of having anemia in patients in the age category below 45 years (OR 1.93, P = 0.013). In conclusion, the study results depict that every additional month in the duration of hemodialysis, age (<45 years), and positive anti-HCV antibody status, these variables were more likely to have anemia in our study MHD patients. While in our final multivariate model, no statistically significant association was observed between hyperparathyroidism and anemia.