Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field.

https://biblio.ugent.be/publication/8555786/file/8555788.pdf

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

In 2009, the Nomenclature Committee on Cell Death (NCCD) proposed a set of recommendations for the definition of distinct cell death morphologies and for the appropriate use of cell death-related terminology, including 'apoptosis', 'necrosis' and 'mitotic catastrophe'. In view of the substantial progress in the biochemical and genetic exploration of cell death, time has come to switch from morphological to molecular definitions of cell death modalities. Here we propose a functional classification of cell death subroutines that applies to both in vitro and in vivo settings and includes extrinsic apoptosis, caspase-dependent or -independent intrinsic apoptosis, regulated necrosis, autophagic cell death and mitotic catastrophe. Moreover, we discuss the utility of expressions indicating additional cell death modalities. On the basis of the new, revised NCCD classification, cell death subroutines are defined by a series of precise, measurable biochemical features.

/pdf/molecular-definitions-of-cell-death-subroutines-q5g428rlyi.pdf

Molecular definitions of cell death subroutines: recommendations of the Nomenclature Committee on Cell Death 2012

Practice guidelines in acute pancreatitis.

https://www.spg.pt/wp-content/uploads/2015/11/2013-ACG_Guideline_AcutePancreatitis_September_2013.pdf

American College of Gastroenterology guideline: management of acute pancreatitis.

Autophagy is a mechanism by which cellular material is delivered to lysosomes for degradation, leading to the basal turnover of cell components and providing energy and macromolecular precursors. Autophagy has opposing, context-dependent roles in cancer, and interventions to both stimulate and inhibit autophagy have been proposed as cancer therapies. This has led to the therapeutic targeting of autophagy in cancer to be sometimes viewed as controversial. In this Review, we suggest a way forwards for the effective targeting of autophagy by understanding the context-dependent roles of autophagy and by capitalizing on modern approaches to clinical trial design.

/pdf/targeting-autophagy-in-cancer-2pjcn0h04a.pdf

Targeting autophagy in cancer

Background: Coronavirus Disease 2019 (COVID-19) pandemic continues unabated in many parts of the world. In the absence of any definite antiviral therapy except some benefit of remdesivir, there is an ongoing search for effective therapy. Famotidine has been shown to reduce mortality in hospitalized patients in a few studies. We conducted a systematic review on the use of famotidine in COVID-19.

Methods: We searched the databases Medline, Embase, Cochrane CENTRAL and Medrxiv. Title/abstract screening, full text screening and data abstraction were carried out in by two reviewers. Case series, cohort studies and randomized trials were included.

Results: Five studies were eligible for inclusion: all were retrospective cohort or case series. Low quality evidence suggests a likely clinical benefit for the use of famotidine in decreasing mortality in hospitalized patients with moderate to severe COVID-19. A meta-analysis of two cohort studies showed a statistically significant decrease in the composite outcome for death and intubation with famotidine (HR 0.44, 95% CI 0.27 to 0.73).

Conclusion: Further evidence from RCTs is required for famotidine to treat COVID 19.

/pdf/efficacy-of-famotidine-for-covid-19-a-systematic-review-and-x0o96zzvau.pdf

Efficacy of Famotidine for COVID-19: A Systematic Review and Meta-analysis

Fluid therapy in acute pancreatitis - aggressive or adequate? Time for reappraisal

Antioxidants for chronic pancreatitis: reasons for disappointing results despite sound principles.

Pancreatic injury is an uncommon and frequently missed injury in abdominal trauma patients. However, missed pancreatic injury is associated with significant morbidity and mortality. This study was conducted to know the burden of pancreatic injury and its outcome in our setup. A retrospective analysis of 53 patients with pancreatic injury from January 2008 through March 2012 at the Jai Prakash Narayan Apex Trauma Center (JPNATC), All India Institute of Medical Sciences (AIIMS), New Delhi. Pancreatic injuries were present in 1.18 % of all trauma admissions. Blunt trauma to the abdomen (n = 49, 92.45 %) due to road traffic injury (n = 38, 71.70 %) was the most common mechanism of injury. Isolated pancreatic injury was present in eight (15.09 %) patients. Grade III pancreatic injury (n = 25, 47 %) was the most common. Of these patients, 18.86 % were managed nonoperatively and 81.13 % were managed operatively. Among the operatively managed patients (n = 43), 74.4 % were operated due to pancreatic injury and 25.5 % were operated due to associated injuries. Distal pancreatectomy with or without spleen preservation (n = 25) was the most common operative procedure done. Three out of five patients of Whipple operation for pancreatic injury died. Pancreatic injury was associated with complications in 43.40 % and death in 20 % (n = 11). Pancreatic injury is rare, but delay in diagnosis of pancreatic injury has been associated with higher morbidity and mortality. Low-grade pancreatic injury with intact main pancreatic duct (MPD) could be successfully managed nonoperatively, whereas in high-grade pancreatic injury, an operative intervention is invariably necessary. Distal pancreatectomy with spleen preservation is a desirable goal whenever possible for distal transaction of the pancreas. Whipple resection should be reserved only for hemodynamically stable patients with complex pancreaticoduodenal injury and is associated with high mortality.

Magnitude, Severity, and Outcome of Traumatic Pancreatic Injury at a Level I Trauma Center in India.

Pancreatic acinar cell necrosis is indicative of severe pancreatitis and the degree of necrosis is an index of its outcome. We studied whether the dose and duration of injury correlates with severity, particularly in terms of necrosis, in caerulein-induced acute pancreatitis (AP) in Swiss albino mice. In addition to control group 1 (G1), groups 2 and 3 received four injections of caerulein every hour but were sacrificed at five hours (G2) and nine hours (G3) respectively, and group 4 received eight injections and was sacrificed at nine hours (G4). The severity of pancreatitis was assessed histopathologically and biochemically. The histopathological scores of pancreatitis in groups 3 and 4 were significantly higher than in groups 1 and 2 (4 vs. 1, 4 vs. 2, 3 vs. 1, 3 vs. 2; P < 0.05). TUNEL-positive apoptotic cells were significantly higher in groups 2 and 3 compared with groups 1 and 4 (P < 0.05). Necrosis was significantly more in group 4 than other groups (37.49% (4.68) vs. 19.97% (1.60) in G2; 20.36% (1.56) in G3; P = 0.006 for G 2 vs. 4 and P = 0.019 for G 3 vs. 4). Electron microscopy revealed numerous autophagosomes in groups 2 and 3 and mitochondrial damage and necrosis in group 4. The pancreatic and pulmonary myeloperoxidase activity in group 4 was significantly higher than that in the other groups (P < 0.01). Hence, severity of pancreatitis is a function of the dose of injurious agent, while inflammation is both dose and duration dependent, which may also explain the wide spectrum of severity of AP seen in clinical practice.

Pramod Kumar Garg

Papers

Efficacy of Famotidine for COVID-19: A Systematic Review and Meta-analysis

Fluid therapy in acute pancreatitis - aggressive or adequate? Time for reappraisal

Antioxidants for chronic pancreatitis: reasons for disappointing results despite sound principles.

Magnitude, Severity, and Outcome of Traumatic Pancreatic Injury at a Level I Trauma Center in India.

Duration of injury correlates with necrosis in caerulein‐induced experimental acute pancreatitis: implications for pathophysiology