Digestive System
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Paquet (Or Modified Paquet that contains 3 categories insted of 4) is the classification used for esophageal varices. Zargar is used for caustic injury

EREFS (EoE reference endoscopic score) is used to grade Eosinophilic esophagitis.

Kodsi is used for staging Candidiasis:

Grade I, a few raised white plaques up to 2 mm in size without edema or ulceration.

Grade II, multiple raised white plaques greater than 2 mm in size without ulceration.

Grade III, confluent, linear, and nodular elevated plaques.

Grade IV, finding of grade III with increased friability of the mucous membranes and occasional narrowing of the lumen

The majority of pancreatic cancers are due to spontaneous mutations in a complex combination of usually several mutations ((KRAS) mutations are common in 90% of pancreatic cancers, but in combination with different other mutations, DNA damage and usually other risk factors.

There is however a very important percentage (5%-10%) of new PC which associate familial pancreatic cancer (Defined by two first-degree-relatives with pancreatic cancer), There are indeed genes involved such as BRCA2 gene  mutations  ( 3.5-fold increased risk of pancreatic cancer ).  Other inherited mutations in the STK11 gene cause the Peutz-Jeghers syndrome, and individuals with Peutz-Jeghers have a 130-fold increased risk of pancreatic cancer

To put in context,

One degree relative with PC  makes relative having an 80% increased risk of developing pancreatic adenocarcinoma (this is RR: 1.8)

individuals with 2 degree relatives with PC have a nine fold risk , and this rises to thirty-two times greater risk if three or more first degree relatives have been previously diagnosed

In the guidelines they mention the increasing resistance of  Hpylori strains in the US to Clarithromycin (20-30%)  and Levofloxacin (approaching 40%) , therfore supporting antibiotics with much lower resistance rates (such as amoxicillin, tetracycline, and rifabutin that are all 5%)

That is why this guidelines say Clarithromycin- and levofloxacin-containing treatment regimens should be avoided in the absence of demonstrated macrolide and quinolone susceptibility, respectively.

Clarithromycin- and levofloxacincontaining treatment regimens remain an important option for selected patients, especially treatment-experienced patients with confirmed persistent H. pylori infection with strains that are known to be susceptible to these antibiotics

Vonoprazan is potassium-competitive acid blocker (PCAB) that inhibits the H⁺, K⁺-ATPase enzyme system in a potassium-competitive manner.    This is the same target as PPI but this class  of drugs  are acid-stable and thus do not require enteric coating or optimal dosing administration 30 minutes prior to meals , are more potent acid suppression, rapid onset of action, and long-lasting half-life.   Penicillin dual therapy was superior to lansoprazole-clarithromycin triple therapy among patients with clarithromycin-resistant H. pylori strains (70% vs 32%, P , 0.0001).

When treating with Vonoprazan + Amoxicillin, exceptionally we can add Clarithromycin as first line even in naive patients.

GERD is a well known risk factor for adenocarcinoma of esophagus, but not for squamous cell carcinoma.

Risk factors for SCC are low socioeconomic status, consumption of tobacco, alcohol, hot beverages, and nitrosamines (e.g cured or smoked) . Additionally, micronutrient deficiencies have also been linked to the development of esophageal squamous cell cancer. These include vitamin C, vitamin E, and folate

Plummer-Vinson syndrome (PVS) is a rare condition characterized by the classic triad of dysphagia, iron-deficiency anemia, and esophageal webbing.  Approximately 10% of patient can develop SCC.

Remember Achalasia as other importart pathology in which there is an increased risk of esophageal cancer, particularly SCC

-Sporadic Pancreatitis: Episode of acute pancreatitis from any ethiology (Ethanol, Obstructive, drug-related..)  There is no strong identified genetic factors. Incidence is 5-12 per 100000

-Idiopathic Pancreatitis: When Acute recurrent pancreatitis (ARP)  on more than one occasion and no cause identified. SPINK1 and CFTR mutations predispose the pancreas to develop pancreatitis from other genetic or environmental factors. It has been  shown that 16%-23% of patients with apparent idiopathic pancreatitis have SPINK1 mutations, compared with only about 2% of healthy controls. Heterozygotes for CFTR mutations are generally healthy but still have a 3 to 4-fold risk over the general population for pancreatitis.

-Autoimmune pancreatitis: THis is an autoimmune condition with type 1 (lymphoplamocytic infiltrate, IgG 4 associated) and 2 segmental or focal narrowing)  As many autoimune conditions, some multi-gene mutations have been described but no specific strong association genetics proved.

-Hereditary pancreatitis :Rare entity that tends to manifest in early ages. HP is a rare cause of acute, recurrent acute, and chronic pancreatitis. Up to 80% of patients with HP have been found to have a mutation in the PRSS1 gene.  A diagnosis  requires (a) demonstration of a clear pattern of autosomal dominant inheritance in a family and/or (b) finding a known disease-causing variant in the PRSS1 gene. This presentation of disease in a family should be consistent with autosomal dominant inheritance – i.e. two or more individuals with recurrent acute or chronic pancreatitis across two or more generations of a family.   Do not confuse with familial pancreatitis, in which  families with a higher incidence of pancreatitis than expected by chance (2 or more 1st or 2nd degree relative with idiophatic pancreatitis)  but no autosomal dominant pattern or PRSS1 is found

Even though only 10% of hep B infections will become chronic and we have an effective vaccination that can virtually prevent infection, the reality is that hepatitis B incidence and prevalence is very high.  WHO estimates that 254 million people were living with chronic hepatitis B infection in 2022, with 1.2 million new infections each year. Maternal-to-newborn perinatal transmission of the virus can be high (70 to 90% in HBeAg-positive-indicating high viral replication-, or 10% to 30% if the mother is HBeAg-negative )

Hepatitis C , despite easy to become chronic (80% of infections) and no effective vaccine, is less common, (Estimated 50 million worldwide) partly because the vertical transmission is low and also because the new  direct-acting antiviral (DAA) tablets are highly effective at clearing the infection in more than 90% , reducing transmission.

Difficult question.  This response is based on Waterfall trial that compared moderate resucitation (1.5ml per Kg) vs aggressive (3ml per Kg) and showed no difference in worsening pancreatitis  but a tendency of fluid overload in the aggresive group (20.5% vs. 6.3%).

Ringer lactate or Hartmanns have been proved to have benefit ovver saline due to an anti-inflammatory effect which was attributed to the properties of lactate and to have a higher pH that can help counteract acidosis.

This indeed is a subject of debate. American guidelines still mentions that most patients with acute pancreatitis & hypovolaemia could have a deficit of 3-4 L to replace in 24h (Like it is our patient with vomiting and  mild hypotension and tachycardia) . If patient has no evidence of hypovolemia, an initial resuscitation rate of no more than 1.5 mL/kg of body weight per hour should be administered. However, in patients with hypovolemia, clinicians should administer a bolus of 10 mL/kg which in this case is 750ml per hour (1500ml in 2 hours)

So, the answer is  Goal-directed rehydration with Ringer’s lactate solution (or Hartmann’s).  In this case of Hypovolemia, our first step should be resucitate until volume is stable (normal BP, HR and clinical status) looking closely to avoid overfluid, and once patient is stable, keep her on 1.5ml per Kg per 24 h with clinical re-checking every few hours to ensure she is not hyper or overhydrated.

Andexanet is factor Xa inhibitor which is approved to reverse Rivaroxaban and Apixaban. However, it has not being proved to be efficacious against Edoxaban. Dabigatran is  a direct thrombin (factor IIa) inhibitor, not a Xa inhibitor.