Consequences of a Surveillance Strategy for Side-Branch Intraductal Pancreatic Mucinous Neoplasms: Long-Term Follow-Up of One-Thousand Cysts.

OBJECTIVE: We aim to quantify the rate of progression in surveilled cysts and assess what factors should indicate delayed resection. SUMMARY BACKGROUND DATA: Side-branch intraductal papillary mucinous neoplasms (SB-IPMNs) are increasingly discovered, making it challenging to identify which patients require resection, thus avoiding inappropriate treatment. Most incidental lesions are surveyed, yet the consequences of that decision remain uncertain. METHODS: A prospectively maintained database of pancreatic cystic neoplasms was queried for patients with SB-IPMN. Patients with ≥2 imaging studies >6 months apart were included. Clinically relevant progression (CR-Progression) was defined by symptoms, worrisome/high-risk stigmata, or invasive cancer (IC). Growth ≥5 mm in 2 years is considered CR-Progression; size ≥3 cm alone is not. RESULTS: Between 1997-2023,1,337 patients were diagnosed with SB-IPMN. Thirty-seven (2.7%) underwent up-front surgery; 1,000 (75.0%) had >6 months surveillance.The rate of CR-progression was 15.3% (n=153) based on size increase (n=63, 6.3%), main-duct involvement (n=48, 4.8%), symptoms (n=8, 5.0%), or other criteria (n=34, 3.4%). At a median follow-up of 6.6 years (IQR 3.0-10.26), 17 patients (1.7%) developed IC. Those with CR-progression developed IC in 11.1% (n=17) and high-grade dysplasia (HGD) in 6.5% (n=10). Nearly half of the cancers were not contiguous with the surveyed SB-IPMN.Size ≥3 cm was not associated with HGD/IC (P=0.232). HGD/IC was least common in CR-progression determined by size growth (6.3%) versus main-duct involvement (24%) or other (43%, P<0.001)Patients with CR-progression demonstrated improved survival (OS) with resection on time-to-event (P<0.001) and multivariate cox-regression (HR=0.205, 0.096-0.439, P<0.001) analyses. OS was not improved with resection in all patients (P=0.244). CONCLUSION: Clinically relevant progression for SB-IPMNs is uncommon with development of cancer anywhere in the pancreas being rare. Initial size should not drive resection. Long-term and consistent non-operative surveillance is warranted, with surgery currently reserved for CR-progression knowing that the majority of these still harbor low grade pathology.

Predicting Mortality Prior to Interhospital Hospital for "Unseen" General Surgery Patients: Development, Validation and Feasibility Trial of a Mortality Risk Calculator.

OBJECTIVE: Develop and validate a mortality risk calculator that could be utilized at the time of transfer, leveraging routinely collected variables that could be obtained by trained non-clinical transfer personnel. SUMMARY BACKGROUND DATA: There are no objective tools to predict mortality at the time of inter-hospital transfer for Emergency General Surgery (EGS) patients that are "unseen" by the accepting system. METHODS: Patients transferred to general or colorectal surgery services from January 2016 through August 2022 were retrospectively identified and randomly divided into training and validation cohorts (3:1 ratio). The primary outcome was admission-related mortality, defined as death during the index admission or within 30 days post-discharge. Multiple predictive models were developed and validated. RESULTS: Among 4,664 transferred patients, 280 (6.0%) experienced mortality. Predictive models were generated utilizing 19 routinely collected variables; the penalized regression model was selected over other models due to excellent performance using only 12 variables. The model performance on the validating set resulted in an area under the receiver operating characteristic curve, sensitivity, specificity, and balanced accuracy of 0.851, 0.90, 0.67, and 0.79, respectively. After bias correction, Brier score was 0.04, indicating a strong association between the assigned risk and the observed frequency of mortality. CONCLUSION: A risk calculator using twelve variables has excellent predictive ability for mortality at the time of interhospital transfer among "unseen" EGS patients. Quantifying a patient's mortality risk at the time of transfer could improve patient triage, bed and resource allocation, and standardize care.

Tumor Size Combined With CA-19 Level Improves Prediction of Survival of Patients With Pancreatic Adenocarcinoma Undergoing Perioperative Chemotherapy and Resection.

BACKGROUND AND OBJECTIVE: Five-year survival in pancreatic adenocarcinoma is less than 20%. While previous studies have postulated that a carbohydrate antigen 19-9 (CA19-9) threshold could predict outcome of resection, the role for CA19-9 in decision-making remains unclear. This study aims to assess whether CA19-9 levels combined with tumor size improve prediction of post-resection survival. METHOD: A retrospective analysis was conducted on 109 patients with pancreatic adenocarcinoma who underwent perioperative chemotherapy followed by resection. The primary outcome of mortality was, divided into short (<1 year) or prolonged (>2 years). Univariate and multivariable analyses compared the tumor size-adjusted CA19-9 between the outcome groups. RESULTS: Twenty-seven (24.78%) and eighty-two (75.23%) patients were in the short survival and prolonged-survival groups, respectively. The mean CA19-9 was significantly greater in the short vs prolonged group (P < .001). Analyzing CA19-9 level by tumor size, the association of high CA19-9 and short survival was significant for small (≤2 cm) and large tumor (>4 cm), but not for intermediate-size tumors (2-4 cm). Adjusting for preoperative variable did not change this association. CONCLUSION: CA 19-9 in combination with tumor size better identifies patients with prolonged post-resection survival. This prediction is most accurate in patients with either small (≤2 cms) or large (>4 cms) tumors compared to intermediate-size tumors.

Gender representation in the Central Surgical Association: A call to action.

BACKGROUND: Organizations such as the Central Surgical Association are important for promulgating advances in general surgery, but diversity and inclusion profoundly affect what is presented and discussed. The objective of this study was to evaluate gender representation trends at the Central Surgical Association and its annual meetings over the past 13 years. METHODS: Publicly available Central Surgical Association meeting proceedings from 2010 to 2022 were reviewed for society leaders, new members, invited speakers and moderators, and contributors to scientific sessions (first authors, senior authors). Gender identity was assessed through professional online platforms. The 2017 and 2021 meetings were conjoined with the Midwest Surgical Association. Incomplete data were obtained from 2013 and 2020-2022. RESULTS: A total of 2,158 individuals were reviewed, 554 (25.7%) of which were women. The overall trend of the absolute proportion of women participation increased by 1.8% per year (R2 = 0.7, P < .01). For leadership roles, 42/205 (20%) were women, with a 2.4% per year increase (R2 = 0.45, P = .02). For speaker roles, 82/384 (21.4%) were women, with a 2.2% increase per year (R2 = 0.6, P < .01). For scientific contributions, 253 first (35.9%) and 136 (19.3%) senior authors of 704 were women, with 1.5% (R2 = 0.4, P = .02) and 1.3% (R2 = 0.4, P = .03) increase per year, respectively. CONCLUSION: There has been a positive trend in women's involvement at Central Surgical Association meetings for leaders, speakers, and scientific authors. Diversity allows variate experiences to contribute to surgical advancements; thus, measures by the Central Surgical Association to ensure adequate representation should continue.

Estimation of shear stress heterogeneity along capillary segments in angiogenic rat mesenteric microvascular networks.

OBJECTIVE: Fluid shear stress is thought to be a regulator of endothelial cell behavior during angiogenesis. The link, however, requires an understanding of stress values at the capillary level in angiogenic microvascular networks. Critical questions remain. What are the stresses? Do capillaries experience similar stress magnitudes? Can variations explain vessel-specific behavior? The objective of this study was to estimate segment-specific shear stresses in angiogenic networks. METHODS: Images of angiogenic networks characterized by increased vascular density were obtained from rat mesenteric tissues stimulated by compound 48/80-induced mast cell degranulation. Vessels were identified by perfusion of a 40 kDa fixable dextran prior to harvesting and immunolabeling for PECAM. Using a network flow-based segment model with physiologically relevant parameters, stresses were computed per vessel for regions across multiple networks. RESULTS: Stresses ranged from 0.003 to 2328.1 dyne/cm2 and varied dramatically at the capillary level. For all regions, the maximum segmental shear stresses were for capillary segments. Stresses along proximal capillaries branching from arteriole inlets were increased compared to stresses along capillaries in more distal regions. CONCLUSIONS: The results highlight the variability of shear stresses along angiogenic capillaries and motivate new discussions on how endothelial cells may respond in vivo to segment-specific microenvironment during angiogenesis.

Angiogenic Microvascular Wall Shear Stress Patterns Revealed Through Three-dimensional Red Blood Cell Resolved Modeling.

The wall shear stress (WSS) exerted by blood flowing through microvascular capillaries is an established driver of new blood vessel growth, or angiogenesis. Such adaptations are central to many physiological processes in both health and disease, yet three-dimensional (3D) WSS characteristics in real angiogenic microvascular networks are largely unknown. This marks a major knowledge gap because angiogenesis, naturally, is a 3D process. To advance current understanding, we model 3D red blood cells (RBCs) flowing through rat angiogenic microvascular networks using state-of-the-art simulation. The high-resolution fluid dynamics reveal 3D WSS patterns occurring at sub-endothelial cell (EC) scales that derive from distinct angiogenic morphologies, including microvascular loops and vessel tortuosity. We identify the existence of WSS hot and cold spots caused by angiogenic surface shapes and RBCs, and notably enhancement of low WSS regions by RBCs. Spatiotemporal characteristics further reveal how fluctuations follow timescales of RBC "footprints." Altogether, this work provides a new conceptual framework for understanding how shear stress might regulate EC dynamics in vivo.

Postoperative Day 1 Drain Amylase After Pancreatoduodenectomy: Optimal Level to Predict Pancreatic Fistula.

INTRODUCTION: Drain amylase on day 1 (DA-D1) after pancreaticoduodendectomy (PD) to predict occurrence of postoperative pancreatic fistula (POPF) is controversial. In this study, we evaluate the optimal DA-D1 level to predict clinically relevant POPF (CR-POPF). METHODS: The 2014-2020 NSQIP pancreatectomy-targeted database was queried for patients who underwent elective PD. Perioperative data was extracted to determine development of POPF and CR-POPF per International Study Group of Pancreatic Fistula guidelines. Receiver operative curve (ROC) and Youden's index were used to assess the performance and optimal cutoff for DA-D1 to predict CR-POPF. The DA-D1 value was confirmed with a multivariable logistic regression to determine hazard ratios (HR) for CR-POPF and conditional logistic regression by modified fistula risk score (mFRS) subgroups. RESULTS: A total of 6,087 patients with complete perioperative data were included. Mean DA-D1 was 2,897 ± 8,636 U/L; median drain duration was 5 days. CR-POPF was documented in 544 (8.9%) patients. DA-D1 ROC for CR-POPF had area under the curve of 0.779 (95%CI 0.759-0.798). Youden's index for the CR-POPF ROC coordinates had 77.6% sensitivity and 66.3% specificity, corresponding to DA-D1 values ≥ 720U/L as an optimal cutoff. CR-POPF was higher for patients with DA-D1 ≥ 720U/L (HR 4.6; p = 0.001). Patients DA-D1 < 720U/L with a negligible, low, intermediate, and high mFRS had respectively 1%, 3%, 4%, and 7% rate of CR-POPF. CONCLUSION: DA-D1 < 720U/L after elective PD is a clinically useful predictor of CR-POPF. For patients with negligible to intermediate FRS, surgeons should consider utilizing DA-D1 < 720 U/L for removal of a drain on the first postoperative day.

The role of minimally invasive surgery in resectable distal pancreatic adenocarcinoma.

BACKGROUND: In distal pancreatectomy (DP) for pancreatic ductal adenocarcinoma (PDAC), we hypothesize that minimally invasive DP (MIDP) carries short-term benefits over ODP (ODP) in the absence of postoperative pancreatic fistula (POPF). METHODS: NSQIP database was queried to select patients who underwent DP for PDAC with available report on POPF. The population was divided into No-POPF vs. POPF groups. In each group, propensity-score matching was applied to compare 30-day outcomes of ODP vs. MIDP. RESULTS: There were 2,824 patients; 2,332 (82%) had No-POPF and 492 (21%) had POPF. In No-POPF patients, 921 pairs were matched between ODP and MIDP. MIDP patients had slightly longer operations (227 vs. 205 minutes; p < 0.001), but lower rates of surgical site complications (1% vs. 2.9%; p = 0.002), postoperative transfusion (7.1% vs. 11.0%; p = 0.003), overall morbidity (21.1% vs. 26.3%; p = 0.009), and one-day shorter median length of stay (LOS) (5 vs. 6 days; p = 0.001). In the POPF group, 172 pairs were matched. There was no difference in morbidity, mortality, reoperation, LOS, and home discharge. Similar conclusions were drawn in the intention-to-treat and per-protocol analyses. CONCLUSION: POPF is common following DP for PDAC. In the absence of POPF, MIDP is associated with fewer postoperative morbidities and shorter LOS.

Evaluating approaches to diagnosis and management of idiopathic acute pancreatitis.

INTRODUCTION: Idiopathic acute pancreatitis (IAP) is a diagnosis of exclusion; systematic work-up is challenging but essential. Recent advances suggest IAP results from micro-choledocholithiasis, and that laparoscopic cholecystectomy (LC) or endoscopic sphincterotomy (ES) may prevent recurrence. METHODS: Patients diagnosed with IAP from 2015-21 were identified from discharge billing records. Acute pancreatitis was defined by the 2012 Atlanta classification. Complete workup was defined per Dutch and Japanese guidelines. RESULTS: A total of 1499 patients were diagnosed with IAP; 455 screened positive for pancreatitis. Most (N = 256, 56.2%) were screened for hypertriglyceridemia, 182 (40.0%) for IgG-4, and 18 (4.0%) MRCP or EUS, leaving 434 (29.0%) patients with potentially idiopathic pancreatitis. Only 61 (14.0%) received LC and 16 (3.7%) ES. Overall, 40% (N = 172) had recurrent pancreatitis versus 46% (N = 28/61) following LC and 19% (N = 3/16) following ES. Forty-three percent had stones on pathology after LC; none developed recurrence. CONCLUSION: Complete workup for IAP is necessary but was performed in <5% of cases. Patients who potentially had IAP and received LC were definitively treated 60% of the time. The high rate of stones on pathology further supports empiric LC in this population. A systematic approach to IAP is lacking. Interventions aimed at biliary-lithiasis to prevent recurrent IAP have merit.

Use of Image Guidance During Pediatric Venovenous Extracorporeal Membrane Oxygenation Cannulation: A Survey of the American Pediatric Surgical Association.

This study evaluated practices for image guidance during placement of bicaval dual-lumen (BCDL) venovenous extracorporeal membrane oxygenation (VV-ECMO) cannulas in pediatric and adolescent patients and elucidates reasoning behind surgeon practices. A survey covering VV-ECMO practice and opinions was distributed by the American Pediatric Surgical Association (APSA) to all attending members. A total of 110 pediatric surgeons responded (11.3%). During initial BCDL cannula placement, 67.7% of surgeons reported using bimodal imaging with either fluoroscopy (38.4%) or x-ray (29.3%) plus echocardiography. Although 37.4% of surgeons used serial x-rays during cannula placement, only 5.9% believed it was best practice to do so ( P < 0.0001). Rather, 60.4% believed that fluoroscopy was the standard. Among surgeons not using fluoroscopy, 27.6% (13.3% of respondents) reported fluoroscopy added unnecessary complexity or that they preferred another modality. More frequently, reasons for not using fluoroscopy are related to resource limitations. Echocardiography use to confirm cannula position was considered best practice by 92.1% of surgeons, with 86.9% utilization. Therefore, most pediatric surgeons use multimodal imaging during cannulation and consider it best practice. Fluoroscopy is preferred, but its use is frequently limited by hospital resources. Echocardiography is widely available and used. These data represent increased consensus among surgeons and present opportunities for modernization of hospital resources and standards.

Discontinuation of the OriGen® Dual-Lumen Right Atrial Cannula Decreased Venovenous ECMO Usage in Neonates and Older Children: A Survey of the American Pediatric Surgical Association.

INTRODUCTION: Dual-lumen cannulas for venovenous (VV)-ECMO are widely used in pediatric patients. The popular OriGen® dual-lumen right atrial cannula was discontinued in 2019 without a comparable replacement. METHODS: A survey covering VV-ECMO practice and opinions was distributed to attending members of the American Pediatric Surgical Association. RESULTS: 137 pediatric surgeons responded (14%). Prior to discontinuation of the OriGen®, 82.5% offered VV-ECMO to neonates, and 79.6% cannulated with the OriGen®. Following its discontinuation, those that offered only venoarterial (VA)-ECMO to neonates increased to 37.6% from 17.5% (p = 0.0002). An additional 33.8% changed their practice to sometimes use VA-ECMO when VV-ECMO was indicated. Reasons for not incorporating dual-lumen bi-caval cannulation into practice included risk of cardiac injury (51.7%), inexperience with bi-caval cannulation in neonates (36.8%), difficulty with placement (31.0%), and recirculation and/or positioning problems (27.6%). For the pediatric/adolescent population, 95.5% of surgeons offered VV-ECMO prior to OriGen® discontinuation. Few switched to exclusive VA-ECMO (1.9%) when the OriGen® was discontinued, but 17.8% of surgeons began to incorporate selective use of VA-ECMO. CONCLUSION: Discontinuation of the OriGen® cannula drove pediatric surgeons to alter their cannulation practices, dramatically increasing VA-ECMO use for neonatal and pediatric respiratory failure. These data may suggest a need for targeted education accompanying major technological shifts. LEVEL OF EVIDENCE: Level IV.

Biliary Anatomy Quiz: Test Your Knowledge.

One of the most common surgical procedures performed in the USA is the cholecystectomy. Understanding biliary anatomy, which includes the gallbladder and extrahepatic biliary tree, is essential for every general surgeon. This quiz includes clinically relevant anatomy and radiology questions for the current and future surgeon at every level of training, and we hope it will be a useful adjunct to one's review.

Long term assessment of antibiotic prophylaxis and biliary microbiome in pancreaticoduodenectomy.

INTRODUCTION: Surgical site infections (SSI) can represent a major complication of pancreaticoduodenectomy (PD). We summarize the outcomes of process improvement efforts to reduce the SSI rates in PD that includes replacing Cefazolin with Ceftriaxone-Metronidazole as antibiotic prophylaxis. Additional efforts included current assessment of biliary microbiome and potential prophylactic failures based on bile cultures and suspected antibiotic allergies. METHOD: A single-center review of PD patients from January-2012 to March-2021. Study groups were divided into Pre and Post May-2015 (Group 1 and 2, respectively) when Ceftriaxone-Metronidazole prophylaxis and routine intraoperative cultures were standardized. Univariate and multivariable analyses were conducted to assess groups' differences and association with SSI. RESULTS: Six hundred ninety patients identified [267(38.7%) and 423(61.3%) in Group 1 and Group2, respectively]. After antibiotic change, SSI rates decreased from 28.1% to 16.5% (incisional: 17.6%-7.5%, organ-space or abscess: 17.2%-13.0%), Group 1 and Group 2, respectively, P<0.001. Ceftriaxone-Metronidazole was used in 75.9% of patients Group 2. When adjusting for other covariates, an SSI-decrease was associated only with Ceftriaxone-Metronidazole (OR 0.34, P<0.001). CONCLUSIONS: Ongoing process improvement has resulted in decreased SSIs with Ceftriaxone-Metronidazole prophylaxis. The benefit of Ceftriaxone-Metronidazole is independent of the biliary microbiome. Improving prophylaxis for those with suspected penicillin allergy is warranted.

Lessons learned and keys to success: Provider experiences during the implementation of virtual oncology tumor boards in the era of COVID-19.

BACKGROUND AND OBJECTIVES: The COVID-19 pandemic required rapid adaptation of multidisciplinary tumor board conferences to a virtual setting; however, there are little data describing the benefits and challenges of using such a platform. METHODS: An anonymous quality improvement survey was sent to participants of tumor board meetings at a large academic institution. Participants answered questions pertaining to the relative strengths and weaknesses of in-person and virtual settings. RESULTS: A total of 335 responses (23.3% response rate) were recorded, and 253 met inclusion criteria. Respondents represented 25 different tumor board meetings, with colorectal, breast, and liver (18.6%, 17.0%, and 13.0%, respectively) being the most commonly attended. Virtual tumor boards were equivalent to in-person across 9 of 10 domains queried, while a virtual format was preferred for participation in off-site tumor boards. The lack of networking opportunities was ranked by physicians to be a significant challenge of the virtual format. Consistent leadership and organization, engaged participation of all attendees, and upgrading technology infrastructure were considered critical for success of virtual meetings. CONCLUSIONS: The implementation of virtual tumor board meetings has been associated with numerous challenges. However, improving several key aspects can improve participant satisfaction and ensure excellent patient care.

Next day discharge after the Nuss procedure using intercostal nerve cryoablation, intercostal nerve blocks, and a perioperative ERAS pain protocol.

BACKGROUND: The Nuss procedure for pectus excavatum has historically been associated with significant postoperative pain, which has been the major factor contributing to hospital length of stay (LOS). METHODS: A single-institution, prospective study of 40 consecutive patients undergoing Nuss bar placement for pectus excavatum between November 2019 and January 2021 was conducted to assess the effectiveness of a multimodality pain management protocol. All patients received T3-T8 intercostal nerve cryoablation (INC), T3-T8 bupivacaine intercostal nerve blocks, Exparel at the skin incisions, and management with a perioperative analgesia regimen that minimized narcotic usage. The primary outcome was LOS. Secondary outcomes included opioid use, pain scores, and time to sensory recovery. RESULTS: 37/40 patients (92.5%) were discharged home on postoperative day (POD) 1, and 3/40 (7.5%) were discharged on POD 2 (mean LOS = 1.1 days). The median average postoperative pain score was 2/10. After eliminating IVPCA from our protocol, total oral morphine equivalent (OME) decreased by 73% (55.5 mg to 15 mg) with no change in pain scores or discharge timing. CONCLUSIONS: INC combined with bupivacaine intercostal nerve blocks and a pre- and post-hospital analgesia protocol facilitated discharge one day after the Nuss procedure, achieved excellent pain control, and eliminated the need for intravenous opioids.

Demographic profile and outcome of patients admitted to a COVID dedicated hospital in Bangladesh during the second wave.

ABSTRACT: In December 2019, with pneumonia-like clinical manifestations, a new severe acute respiratory syndrome coronavirus 2 emerged and quickly escalated into a pandemic. Since the first case detected in early March of last year, 8668 have died with an infection mortality rate of 1.52%, as of March 20, 2021. Bangladesh has been struck by the 2nd wave from mid-march 2021. As data on the second wave are sparse, the present study observed the demographic profile, symptoms, and outcomes of Coronavirus Disease 2019 (COVID-19) patients during this wave.The study was conducted at Sheikh Russel National Gastroliver Institute on 486 admitted cases during the 2nd wave of COVID-19 in Bangladesh (March 24-April 24, 2021) using a cross-sectional study design and a convenient sampling technique.Out of 486 cases, 306 (62.9%) were male, and 180 were female, with a mean age of 53.47 ±â€Š13.86. The majority of patients (32.5%) were between the ages of 51 and 60. While fever and cough being the predominant symptoms (>70% cases), the most common co-morbidities were hypertension (41.4) and diabetes mellitus (39.4). Intensive care unit utilization rate was 25%, and a half of the patients had 51% to 70% tomographic lung involvement with an overall mortality rate of 19.3%. Older age, chronic renal disease, percentage of lung involvement, and intensive care unit necessity were important mortality determinants.The present study gives an insight into the demographic profiles and outcomes of admitted patients with COVID-19 during the second wave at a covid dedicated hospital in Bangladesh.

Perception, Preventive Practice, and Attitude Towards Vaccine Against COVID-19 Among Health Care Professionals in Bangladesh.

BACKGROUND: Healthcare professionals (HCPs) are one of the vital and persuading means of information, prevention and control, and incentive of vaccination to content a pandemic. Therefore, knowing the status of HCPs' perception about symptoms, transmission, preventive measures, and attitudes towards a vaccine against COVID-19 is crucial. METHODS: This multi-center cross-sectional descriptive study was one of the first and foremost ones in Bangladesh among the HCPs - doctors, nurses, and other subordinates (MLSS) engaged at COVID-dedicated hospitals. The study was conducted from February 5, 2021, to March 7, 2021, using a convenience sampling method among 550 HCPs using structured questionnaire with twenty-five questions on a three-point scale of responses. RESULTS: The age range of the respondents were 18 to 64 years with the mean 36.17 ±10.94 years of 524 HCPs, of which the majority of the respondents were female 323 (61.6%) and 201 (38.4%) were male with the 95.27% response rate. Almost all participants had "high" or more than sufficient perception (94.34%) about the symptoms of COVID-19. But all categories of HCPs expressed their poor or fair practice about restraining from shaking hands, and only 6.84% of nurses, 8.33% doctors, and 11.59% of MLSS avoided crowded public gatherings as a practice of prevention. A majority (95.99%) of the HCPs showed positive attitudes about the availability of vaccines free of cost, and 87.40% showed trust in the efficacy and safety of the vaccine against COVID-19. CONCLUSION: The majority of the HCPs from the COVID-dedicated hospitals have a good perception and positive attitude towards vaccination; nevertheless, have a poor practice of prevention toward COVID-19. This may play a vital role in motivation and wide acceptance of vaccine among the general population and contribute in comprehensive strategic planning to fight back against the pandemic in the country with the restricted resource.

Neuronal Pentraxin 1 Promotes Hypoxic-Ischemic Neuronal Injury by Impairing Mitochondrial Biogenesis via Interactions With Active Bax[6A7] and Mitochondrial Hexokinase II.

Mitochondrial dysfunction is a key mechanism of cell death in hypoxic-ischemic brain injury. Neuronal pentraxin 1 (NP1) has been shown to play crucial roles in mitochondria-mediated neuronal death. However, the underlying mechanism(s) of NP1-induced mitochondrial dysfunction in hypoxia-ischemia (HI) remains obscure. Here, we report that NP1 induction following HI and its subsequent localization to mitochondria, leads to disruption of key regulatory proteins for mitochondrial biogenesis. Brain mitochondrial DNA (mtDNA) content and mtDNA-encoded subunit I of complex IV (mtCOX-1) expression was increased post-HI, but not the nuclear DNA-encoded subunit of complex II (nSDH-A). Up-regulation of mitochondrial proteins COXIV and HSP60 further supported enhanced mtDNA function. NP1 interaction with active Bax (Bax6A7) was increased in the brain after HI and in oxygen-glucose deprivation (OGD)-induced neuronal cultures. Importantly, NP1 colocalized with mitochondrial hexokinase II (mtHKII) following OGD leading to HKII dissociation from mitochondria. Knockdown of NP1 or SB216763, a GSK-3 inhibitor, prevented OGD-induced mtHKII dissociation and cellular ATP decrease. NP1 also modulated the expression of mitochondrial transcription factor A (Tfam) and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), regulators of mitochondrial biogenesis, following HI. Together, we reveal crucial roles of NP1 in mitochondrial biogenesis involving interactions with Bax[6A7] and mtHKII in HI brain injury.

ZNF410 represses fetal globin by singular control of CHD4.

Known fetal hemoglobin (HbF) silencers have potential on-target liabilities for rational ß-hemoglobinopathy therapeutic inhibition. Here, through transcription factor (TF) CRISPR screening, we identify zinc-finger protein (ZNF) 410 as an HbF repressor. ZNF410 does not bind directly to the genes encoding γ-globins, but rather its chromatin occupancy is concentrated solely at CHD4, encoding the NuRD nucleosome remodeler, which is itself required for HbF repression. CHD4 has two ZNF410-bound regulatory elements with 27 combined ZNF410 binding motifs constituting unparalleled genomic clusters. These elements completely account for the effects of ZNF410 on fetal globin repression. Knockout of ZNF410 or its mouse homolog Zfp410 reduces CHD4 levels by 60%, enough to substantially de-repress HbF while eluding cellular or organismal toxicity. These studies suggest a potential target for HbF induction for ß-hemoglobin disorders with a wide therapeutic index. More broadly, ZNF410 represents a special class of gene regulator, a conserved TF with singular devotion to regulation of a chromatin subcomplex.