The role of computed tomography in acute bowel obstruction due to a supravesical hernia: a case report from Nepal.

Introduction and importance: Supravesical hernias are rare internal hernias but potential cause of small-bowel obstruction. The clinical features are often non-specific, preoperative diagnosis is very difficult and is often diagnosed intraoperatively. The exact pathogenesis is unclear with the major risk factors of prematurity, a positive family history, male sex, smoking habits leading to decreased collagen production, advancing age, and conditions characterized by defective collagen synthesis. Case presentation: The authors are reporting a case of small-bowel obstruction secondary to a supravesical hernia, in a 78-year-old male presented with central abdominal pain, vomiting and obstipation. Ultrasonography of the abdomen and pelvis identified a marked dilation of the small-bowel loop with multiple loops of dilated jejunum and ileum in contrast-enhanced computed tomography (CT) scan of the abdomen and pelvis with lead point from the terminal ileum. Exploratory laparotomy was done with the diagnosis of left posterior a left posterior superior vesical hernia with small-bowel obstruction. Clinical discussion: The case focuses supravesical hernia as a rare yet life-threatening etiology of small-bowel obstruction, emphasizing the importance of clinical suspicion when patients present with signs and symptoms of bowel obstruction. While diagnosis often occurs intraoperatively, the utilization of CT scans in emergency settings can provide valuable insights into the location, potential causes, and condition of the herniated bowel sac. The case highlights the pivotal role of CT scans in diagnosis and emphasizes the need for multidisciplinary cooperation among clinicians, radiologists, and surgeons. Conclusion: Early intervention ensures better outcomes and prevents irreversible bowel damage, underscoring the importance of a comprehensive approach to patient care.

Safety monitoring of precautionary third dose of COVID-19 vaccines in a district in Northern India.

Background: The World Health Organization (WHO) declared Coronavirus disease-19 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) a pandemic on March 11, 2020. On 16th January 2021, India began its vaccination programme using two COVID-19 vaccines (Covishield and Covaxin). Precautionary dose (booster shots) was administered to health and front-line workers in the beginning and then to all eligible populations. Material and Methods: This was a descriptive observational study conducted in the COVID-19 vaccination centres of Karnal district and the ADR monitoring centre, KCGMC, Karnal. During the visits to vaccination centres, all beneficiaries of the precautionary third dose of COVID-19 vaccines as well as healthcare workers were sensitized to report in case of any adverse event following vaccination as part of the policy of the vaccination programme run by the government and Pharmacovigilance Programme of India. The data were collected in suspected adverse drug reaction (ADR) reporting form version 1.4, and causality assessment was done as per the WHO-UMC scale. The data were analysed as simple proportions and percentages. Results: The booster dose was administered to 72,853 individuals, while the 1st dose and 2nd dose were given to 13,30,042 and 10,73,050, respectively. Only three ADRs were reported with the booster dose in 34 vaccination centres in the Karnal district. These three ADRs were classified as unlikely on causality assessment and hence not included in the analysis. Conclusion: The booster dose administered for the prevention of COVID-19 has been found to be reasonably safe. The population who received COVID-19 booster doses was significantly less than the populations who received the first and second doses, which suggests a low acceptance rate.

Area-Selective Atomic Layer Deposition of Ru Using Carbonyl-Based Precursor and Oxygen Co-Reactant: Understanding Defect Formation Mechanisms.

Area selective deposition (ASD) is a promising IC fabrication technique to address misalignment issues arising in a top-down litho-etch patterning approach. ASD can enable resist tone inversion and bottom-up metallization, such as via prefill. It is achieved by promoting selective growth in the growth area (GA) while passivating the non-growth area (NGA). Nevertheless, preventing undesired particles and defect growth on the NGA is still a hurdle. This work shows the selectivity of Ru films by passivating the Si oxide NGA with self-assembled monolayers (SAMs) and small molecule inhibitors (SMIs). Ru films are deposited on the TiN GA using a metal-organic precursor tricarbonyl (trimethylenemethane) ruthenium (Ru TMM(CO)3) and O2 as a co-reactant by atomic layer deposition (ALD). This produces smooth Ru films (<0.1 nm RMS roughness) with a growth per cycle (GPC) of 1.6 Å/cycle. Minimizing the oxygen co-reactant dose is necessary to improve the ASD process selectivity due to the limited stability of the organic molecule and high reactivity of the ALD precursor, still allowing a Ru GPC of 0.95 Å/cycle. This work sheds light on Ru defect generation mechanisms on passivated areas from the detailed analysis of particle growth, coverage, and density as a function of ALD cycles. Finally, an optimized ASD of Ru is demonstrated on TiN/SiO2 3D patterned structures using dimethyl amino trimethyl silane (DMA-TMS) as SMI.

A rare case of retained metallic foreign body in liver: case report and review of literature.

Introduction and importance: Foreign bodies in the liver are uncommon but can lead to severe conditions like liver abscess and sepsis. They typically enter through direct penetration, migration from the gastrointestinal tract, or through the blood. Common foreign objects include metal pins, or sewing needles swallowed accidentally. Case presentation: A 25-year-old male presented to our OPD with pain over the right abdomen with a prior history of projectile injury causing laceration over the right anterior abdomen with primary suturing. On radiological investigation, a retained foreign body was revealed. The metallic foreign body was embedded in the liver for 5 months. Removal of the foreign body was performed without any complications. Clinical discussion: Intrahepatic foreign bodies (FBs) in the liver can result from penetrating injuries, iatrogenic causes, or ingestion, particularly in children. Clinical presentations vary, and complications such as abscess formation may occur. Diagnosis involves imaging modalities like X-rays, ultrasonography, and computed tomography (CT) scans. The presented case highlights the importance of meticulous follow-up, as chronic pain manifested despite conservative management. The management of intrahepatic FBs depends on factors like size, location, and symptoms, with conservative approaches for stable patients. Surgical removal remains the mainstay of the treatment. Long-term monitoring is crucial to detect potential complications, and imaging studies play a key role in regular follow-up. Conclusion: Hepatic foreign bodies are rare, and symptoms vary based on size, type, and location, ranging from asymptomatic to complications such as abscess formation. Surgical removal is the main treatment, but in cases of noncomplicated hepatic foreign bodies, close follow-up is necessary.

Evaluating Static Bone Cysts (SBCs) Through Long-Term Volumetric Analysis Using CBCT: A Study with 6-Month Follow-Up.

Background: Salivary gland bone defects are static lesions which are rare entities, generally asymptomatic and found in routine imaging exams. However, in atypical cases or when misdiagnosed, surgical intervention is carried out. Purpose: a) The study is intended to investigate the frequency of SBC's and to describe the radiological characteristics of its subtypes; b) To evaluate the efficacy of volumetric analysis tool in CBCT and; c) To describe the confirmative role of CBCT in the diagnosis of SBC's without the need for surgical intervention. Material and Methods: The study was conducted on 11 subjects with SBC detected on 3304 panoramic radiographs. CBCT images for each patient were captured at baseline and at an interval of 6 months. Radiographic sub-types of SBC based on the relationship to mandibular canal and bucco-lingual expansion were studied. Files in DICOM format were transferred into OnDemand 3D program (Cybermed Co, Seoul, Korea) and volumes in mm3 of the cavities were measured by 2 observers at both intervals. Inter and intra reliability of volumetric measurements between observers was compared using correlation coefficient and student t test. Results: There were 8 males and 3 females who had SBC in this study (age range: 22-70 years). According to the relationship of SBC with mandibular canal, most SBCs were Type 1 (63.5 %) followed by Type 2 & 3 (18.5 %) each. The total volume of SBC in patients ranged from 146 mm3 to 650 mm3 (mean: 332.5 mm3). There was no significant difference between observers for volume measurements at baseline and at 6 months interval (p>0.05). Conclusions: Based on the results of this study, CBCT should be considered as a definitive diagnostic modality for volumetric analysis of SBCs. Over diagnosis, unnecessary surgical exploration and agony to patients can be avoided using this tool. Key words:Stafne bone cavity, CBCT, Volumetric analysis, salivary gland, panoramic radiography.

Presentation, management and outcomes of iliopsoas abscess at a University Teaching Hospital in Nepal.

Objectives: Iliopsoas abscess (IPA) is an uncommon clinical disease and is often missed to diagnose due to vague clinical presentation. Early treatment with drainage and appropriate antibiotic therapy is necessary before sepsis sets in and become lethal. We conducted this study to evaluate clinical features, etiology, management strategies, and outcomes in patients with IPA from a University Teaching Hospital in Nepal. Methods: A retrospective analysis of 32 consecutive IPA cases managed at Tribhuvan University Teaching Hospital, Nepal for the period of January 2019 to February 2022 was carried out. Results: The mean age was 42.5 ± 19.1 years (range, 19-75 years) and the male: female ratio was 2.2:1. Two-thirds or more patients presented with fever, limp, fixed flexion deformity and/or low back pain. Ultrasonography (US) was diagnostic in 27 (84.4%) patients. Eighteen (56.3%) patients had primary IPAs, and 14 (43.7%) had secondary IPAs. Thirty (93.7%) patients were managed with US guided percutaneous drainage (PCD) and 2 (6.2%) patients underwent open surgical drainage. Drainage procedures were combined with antibiotics in all patients. Pus culture showed Staphylococcus aureus growing in the majority of cases (10 of 23, 43.5%). The hospital stay was longer in patients treated via surgical drainage compared to those who received PCD: 13 days (range 12-14 days) vs. 6.6 days (range 4-13 days), respectively. Recurrence of abscess was seen in 4 (12.5%) cases and all were successfully managed via a second PCD. There was no mortality. Conclusions: Varying clinical presentation of iliopsoas abscess demand a high index of suspicion for early diagnosis. Initial imaging modality in suspected case of IPA is US. US-guided PCD along with the appropriate antibiotics is a successful frontline treatment of IPAs with shorter hospital stay.

Utilization rates of intravenous thrombolysis for acute ischemic stroke in Asian countries:: A systematic review and meta-analysis.

BACKGROUND: Despite intravenous thrombolysis (IVT) being used for the treatment of acute ischemic stroke (AIS) for over two decades, its accessibility remains limited in various regions of the world. The Asian region, which experiences the highest age-standardized incidence of AIS, currently lacks comprehensive data on the utilization of IVT. AIMS: This study aimed to provide precise estimates of IVT usage for AIS in Asian countries. METHODS: A literature search was conducted on PubMed and Google using appropriate search terms. English language, peer reviewed articles published after 2010 were included in the analysis. The pooled proportion was calculated utilizing the DerSimonian and Laird random-effects model. Additionally, a subgroup analysis was conducted, taking into account factors such as the study's country, the economic status of the country, specific Asian regions, publication year (before 2015 and from 2015 onwards), study location, study setting, hospital stroke protocol, and national stroke guidelines. RESULTS: 67 observational studies with 778,046 patients with AIS were included in the meta-analysis. The overall utilization rate of IVT was found to be 9.1%. High-income countries had a higher rate (11.3%) compared to lower-middle-income (8.1%) and upper-middle-income countries (9%). Central and North Asia had the highest rate (17.5%) and Southeast Asia had the lowest rate (6.8%). Studies conducted after 2015 had a higher thrombolysis rate (11.3%) compared to those before 2015 (1.5%). Presence of hospital stroke protocols (10.7%) and national stroke guidelines (10.1%) were associated with higher thrombolysis rates. CONCLUSION: The overall utilization rate of IVT for AIS in Asia stood at 9.1%, showcasing noteworthy disparities across countries, regions, and income brackets. To improve thrombolysis rates in the region, addressing prehospital delays, increasing public awareness, and implementing stroke protocols and national guidelines are key strategies.

Comparing High- and Low-Model for End-Stage Liver Disease Living-Donor Liver Transplantation to Determine Clinical Efficacy: A Systematic Review and Meta-Analysis (CHALICE Study).

INTRODUCTION: Various studies have demonstrated that low-Model for End-Stage Liver Disease (MELD) living-donor liver transplant (LDLT) recipients have better outcomes with improved patient survival than deceased-donor liver transplantation (DDLT) recipients. LDLT recipients gain the most from being transplanted at MELD <25-30; however, some existing data have outlined that LDLT may provide equivalent outcomes in high-MELD and low-MELD patients, although the term "high" MELD is arbitrarily defined in the literature and various cut-off scores are outlined between 20 and 30, although most commonly, the dividing threshold is 25. The aim of this meta-analysis was to compare LDLT in high-MELD with that in low-MELD recipients to determine patient survival and graft survival, as well as perioperative and postoperative complications. METHODS: Following PROSPERO registration CRD-42021261501, a systematic database search was conducted for the published literature between 1990 and 2021 and yielded a total of 10 studies with 2183 LT recipients; 490 were HM-LDLT recipients and 1693 were LM-LDLT recipients. RESULTS: Both groups had comparable mortality at 1, 3 and 5 years post-transplant (5-year HR 1.19; 95% CI 0.79-1.79; p-value 0.40) and graft survival (HR 1.08; 95% CI 0.72, 1.63; p-value 0.71). No differences were observed in the rates of major morbidity, hepatic artery thrombosis, biliary complications, intra-abdominal bleeding, wound infection and rejection; however, the HM-LDLT group had higher risk for pulmonary infection, abdominal fluid collection and prolonged ICU stay. CONCLUSIONS: The high-MELD LDLT group had similar patient and graft survival and morbidities to the low-MELD LDLT group, despite being at higher risk for pulmonary infection, abdominal fluid collection and prolonged ICU stay. The data, primarily sourced from high-volume Asian centers, underscore the feasibility of living donations for liver allografts in high-MELD patients. Given the rising demand for liver allografts, it is sensible to incorporate these insights into U.S. transplant practices.

Hepatogastric fistula: a complication of pyogenic liver abscess in a patient with the Brugarda syndrome - A rare case report.

Hepatogastric fistula following pyogenic liver abscess (PLA) is a rare and fatal complication, and only a handful of cases have been reported without co-existing comorbidities of Brugarda syndrome. Case presentation: A 22-year-old male presented to the emergency room with a known case of Brugarda pattern ECG with chief complaints of on-and-off abdominal pain and fever for 2 weeks and shortness of breath for one day. On evaluation, echocardiography showed a clot in the inferior vena cava (IVC) and right atrium (RA), and on computed tomography scan of the abdomen revealed a liver abscess with transmural gastric perforation. During, an exploratory laparotomy where a fistula joining the left lobe of the liver and stomach was detected, and an emergency excision was done. The patient was shifted to the ICU and later developed septic shock, which was managed medically. Clinical discussion: Usually, thrombosis of the portal vein and the hepatic vein is a very common complication of a PLA but vascular complications like IVC, RA thrombosis, and hepatogastric fistula have been reported rarely. Our case is peculiar hepatogastric fistulization along with IVC/RA clots in a patient with Brugarda pattern ECG. The typical clinical manifestation of a patient with hepatogenic fistula is absent in our patient and presented with an on-off type of fever, epigastric pain, and shortness of breath and was managed surgically. Conclusion: Hepatogasric fistula, thrombosis of the IVC, and RA are a rare complications of PLA. The patient with Brugarda syndrome is at high risk as its clinical manifestation gets exaggerated during sepsis.

Infected pancreatic necrosis: outcomes and clinical predictors of mortality. A post hoc analysis of the MANCTRA-1 international study.

The identification of high-risk patients in the early stages of infected pancreatic necrosis (IPN) is critical, because it could help the clinicians to adopt more effective management strategies. We conducted a post hoc analysis of the MANCTRA-1 international study to assess the association between clinical risk factors and mortality among adult patients with IPN. Univariable and multivariable logistic regression models were used to identify prognostic factors of mortality. We identified 247 consecutive patients with IPN hospitalised between January 2019 and December 2020. History of uncontrolled arterial hypertension (p = 0.032; 95% CI 1.135-15.882; aOR 4.245), qSOFA (p = 0.005; 95% CI 1.359-5.879; aOR 2.828), renal failure (p = 0.022; 95% CI 1.138-5.442; aOR 2.489), and haemodynamic failure (p = 0.018; 95% CI 1.184-5.978; aOR 2.661), were identified as independent predictors of mortality in IPN patients. Cholangitis (p = 0.003; 95% CI 1.598-9.930; aOR 3.983), abdominal compartment syndrome (p = 0.032; 95% CI 1.090-6.967; aOR 2.735), and gastrointestinal/intra-abdominal bleeding (p = 0.009; 95% CI 1.286-5.712; aOR 2.710) were independently associated with the risk of mortality. Upfront open surgical necrosectomy was strongly associated with the risk of mortality (p < 0.001; 95% CI 1.912-7.442; aOR 3.772), whereas endoscopic drainage of pancreatic necrosis (p = 0.018; 95% CI 0.138-0.834; aOR 0.339) and enteral nutrition (p = 0.003; 95% CI 0.143-0.716; aOR 0.320) were found as protective factors. Organ failure, acute cholangitis, and upfront open surgical necrosectomy were the most significant predictors of mortality. Our study confirmed that, even in a subgroup of particularly ill patients such as those with IPN, upfront open surgery should be avoided as much as possible. Study protocol registered in ClinicalTrials.Gov (I.D. Number NCT04747990).

Minimal access surgery of corrosive and thermal strictures of the foregut.

Background and Aim: : Conventional surgery for caustic/thermal strictures (CS/TS) entails considerable trauma, which may be mitigated by minimal access surgery (MAS). Experience with its use in CS/TS is both heterogeneous and limited, hence, warrants a comprehensive review. Methods: : Medical literature/indexing databases were systematically searched for pertinent articles published in English, from 1990 to 2021, and analysed. Results: : Fifty relevant articles, pertaining to over 200 patients, were found. They showed that MAS is feasible in CS/TS management. It reduces the access damage in chest and abdomen whilst facilitating resection or bypass of the affected gut segment through different combination of operations, sequence of steps, conduits and routes. The procedures range from completely minimal access to hybrid ones, with reduced complications and faster recovery. Hybrid procedures prove as expeditious as open ones. Conclusions: : MAS proves efficacious in restoring alimentary continuity in corrosive/thermal strictures of the foregut.

Management of diabetic dyslipidemia in Indians: Expert consensus statement from the Lipid Association of India.

In 2021 an estimated 74 million individuals had diabetes in India, almost all type 2 diabetes. More than half of patients with diabetes are estimated to be undiagnosed and more 90% have dyslipidemia that is associated with accelerated development of atherosclerotic cardiovascular disease (ASCVD). Patients of Indian descent with diabetes have multiple features that distinguish them from patients with diabetes in Western populations. These include characteristics such as earlier age of onset, higher frequency of features of the metabolic syndrome, more prevalent risk factors for ASCVD, and more aggressive course of ASCVD complications. In light of the unique features of diabetes and diabetic dyslipidemia in individuals of Indian descent, the Lipid Association of India developed this expert consensus statement to provide guidance for management of diabetic dyslipidemia in this very high risk population. The recommendations contained herein are the outgrowth of a series of 165 webinars conducted by the Lipid Association of India across the country from May 2020 to July 2021, involving 155 experts in endocrinology and cardiology and an additional 2880 physicians.

Cervical vagal schwannoma, a rare differential of a neck swelling: A case report.

Cervical vagal schwannoma is a rare clinical entity that requires a different clinical approach than other neck swellings. Magnetic resonance imaging is the preferred initial diagnostic test. Complications may arise due to vagal stimulation in unsuspecting open biopsies. Surgical excision with perioperative vagal monitoring is recommended for the treatment of vagal schwannomas.

Biliary Cripple and the Spectrum of Complications following Cholecystectomy: A Case Report.

Bile duct injury is a complication seen during cholecystectomy. Here, we highlight the occurrence of bile duct injury (BDI) during an open cholecystectomy who underwent hepaticojejunostomy (HJ), later presenting with a stricture of HJ. Percutaneous transhepatic biliary drainage (PTBD) was performed which led to the development of hepatic artery injury.

Safety and efficacy of low-cost alternative urokinase in acute ischemic stroke: A systematic review and meta-analysis.

INTRODUCTION: Use of intravenous thrombolysis (IVT) for treatment of acute ischemic stroke (AIS) varies greatly between countries, ranging from 10% to 15% in high-income countries to less than 2% in low- and middle income countries (LMICs). This is because alteplase is expensive and has been cited as one of the most common barriers to IVT in LMICs. Urokinase (UK) is a thrombolytic agent which is almost 50 times cheaper with easier production and purification than alteplase. UK may become a cost-effective option for IVT in LMICs if it is found to be safe and effective. We conducted this study to assess the existing evidence on the safety and efficacy of UK vs alteplase for IVT in AIS. METHODS: The study was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and meta-Analyses) guideline. Systematic literature search was done in PubMed, EMBASE, and Google Scholar for English literature published from 2010 to 2021. RESULTS: A total of 4061 participants in the alteplase and 2062 participants in the UK group were included in the final statistical analysis. After IVT, a good functional outcome at last follow-up was found among 80.57 % of patients in the alteplase group compared to 73.79 % of patients in the UK group (OR: 1.11; 95 % CI: 0.95- 1.31; I2 = 0 %; P = 0.18). Symptomatic Intracerebral Hemorrhage (sICH) was found among 1.77 % of patients in the alteplase group compared to 2.83 % of patients in the UK group (OR: 0.84; 95 % CI: 0.56- 1.26; I2 = 0 %; P = 0.41). Similarly, mortality was found among 5.03 % of patients in the alteplase group compared to 5.42 % of patients in the UK group (OR: 0.87; 95 % CI: 0.66-1.14; I2 = 0 %; P = 0.30). CONCLUSION: Our meta-analysis found that intravenous UK is not inferior to alteplase in terms of safety and efficacy and can be a viable alternative for IVT in AIS patients in LMICs.

Amyotrophic lateral sclerosis and retinal changes in optical coherence tomography: A systematic review and meta-analysis.

INTRODUCTION: Increasing evidence suggests Amyotrophic Lateral Sclerosis (ALS) as a widespread pathological process comprising nonmotor features like fatigue, mild sensory symptoms, cognitive decline, and visual impairment. Measurements of retinal nerve fiber layer (RNFL) thickness using Optical Coherence Tomography (OCT) may correlate with the neurodegeneration associated with ALS. In addition to RNFL thickness, other OCT parameters have been explored in the context of diagnosing ALS and predicting disease severity. In this study, we explore the possibility that OCT parameters of patients with ALS may differ significantly from those of healthy controls and thus serve as biomarkers for the disease and its progression. MATERIALS AND METHODS: Between 2010 and 2021, the PubMed and EMBASE databases were examined for English language literature. ALS severity was assessed using the revised ALS functional rating scale (ALSFRS-R). The pooled mean differences in RNFL thickness between ALS patients and controls were calculated using the Standard Mean Difference (Hedges's g) with a 95% confidence interval (CI) in STATA software version 16. RESULTS: Eleven studies were reviewed for data collection. RNFL thickness was not statistically significantly different between ALS patients (n = 412) and controls (n = 376) (Hedges's g = -0.22; 95% CI: -0.51 to 0.07, I2 = 73.04%, p = .14). However, the thickness of inner nuclear layer was significantly different between ALS patients and controls (Hedges's g = -0.38; 95% CI: -0.61 to 0.14, I2 = 14.85%, p = .00). CONCLUSION: Our meta-analysis found that RNFL thickness as a whole or by individual quadrants was not significantly different between ALS patients and controls while the inner nuclear layer (INL) was substantially thinner.

Therapeutic drug level of tacrolimus causing intracranial hemorrhage in a patient with renal transplant.

Tacrolimus is used in solid organ transplant patients to prevent rejection, and no case of intracerebral hemorrhage (ICH) has been reported till date. We report a case of 31-year-old man with diabetes and hypertension for ten years who had a renal transplant four years back; diagnosed with tacrolimus-induced ICH.

Mechanistic insights of key host proteins and potential repurposed inhibitors regulating SARS-CoV-2 pathway.

The emergence of pandemic situations originated from severe acute respiratory syndrome (SARS)-CoV-2 and its new variants created worldwide medical emergencies. Due to the non-availability of efficient drugs and vaccines at these emergency hours, repurposing existing drugs can effectively treat patients critically infected by SARS-CoV-2. Finding a suitable repurposing drug with inhibitory efficacy to a host-protein is challenging. A detailed mechanistic understanding of the kinetics, (dis)association pathways, key protein residues facilitating the entry-exit of the drugs with targets are fundamental in selecting these repurposed drugs. Keeping this target as the goal of the paper, the potential repurposing drugs, Nafamostat, Camostat, Silmitasertib, Valproic acid, and Zotatifin with host-proteins HDAC2, CSK22, eIF4E2 are studied to elucidate energetics, kinetics, and dissociation pathways. From an ensemble of independent simulations, we observed the presence of single or multiple dissociation pathways with varying host-proteins-drug systems and quantitatively estimated the probability of unbinding through these specific pathways. We also explored the crucial gateway residues facilitating these dissociation mechanisms. Interestingly, the residues we obtained for HDAC2 and CSK22 are also involved in the catalytic activity. Our results demonstrate how these potential drugs interact with the host machinery and the specific target residues, showing involvement in the mechanism. Most of these drugs are in the preclinical phase, and some are already being used to treat severe COVID-19 patients. Hence, the mechanistic insight presented in this study is envisaged to support further findings of clinical studies and eventually develop efficient inhibitors to treat SARS-CoV-2.

Laparoscopic versus open colectomy for locally advanced T4 colonic cancer: meta-analysis of clinical and oncological outcomes.

BACKGROUND: The aim of this study was to review the early postoperative and oncological outcomes after laparoscopic colectomy for T4 cancer compared with open surgery. METHOD: MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched for any relevant clinical study comparing laparoscopic and open colectomy as treatment for T4 colonic cancer. The risk ratio (RR) with 95 per cent c.i. was calculated for dichotomous variables, and the mean difference (m.d.) with 95 per cent confidence interval for continuous variables. Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was implemented for assessing quality of evidence (QoE). RESULTS: Twenty-four observational studies (21 retrospective and 3 prospective cohort studies) were included, analysing a total of 18 123 patients: 9024 received laparoscopic colectomy and 9099 underwent open surgery. Laparoscopic colectomy was associated with lower rates of mortality (RR 0.48, 95 per cent c.i. 0.41 to 0.56; P < 0.001; I2 = 0 per cent, fixed-effect model; QoE moderate) and complications (RR 0.61, 0.49 to 0.76; P < 0.001; I2 = 20 per cent, random-effects model; QoE very low) compared with an open procedure. No differences in R0 resection rate (RR 1.01, 1.00 to 1.03; P = 0.12; I2 = 37 per cent, random-effects model; QoE very low) and recurrence rate (RR 0.98, 0.84 to 1.14; P = 0.81; I2 = 0 per cent, fixed-effect model; QoE very low) were found. CONCLUSION: Laparoscopic colectomy for T4 colonic cancer is safe, and is associated with better clinical outcomes than open surgery and similar oncological outcomes.

Colonic cancer is a common condition, and in 10-20 per cent of patients the tumour has grown beyond the bowel wall or invaded other organs at diagnosis (called locally advanced colonic cancer). This study reviews the use of laparoscopic (minimally invasive surgery or keyhole surgery) to treat these locally advanced tumours. Medical databases were searched for research publications on the subject. In total, 24 studies (including data on 18 123 patients) comparing laparoscopic with traditional open surgery were identified. Analysing the data of the studies together found that laparoscopic surgery was associated with lower rates of mortality and surgical complications. No difference in survival or cancer recurrence was found.