December bimonthly exam

December 17, 2020

December bimonthly exam

Question no. 1

Q. 1) A 55 year old man with Recurrent Focal Seizures

Detailed patient case report here: http://ushaindurthi.blogspot.com/2020/11/55-year-old-male-with-complaints-of.html

1. What is the problem representation of this patient and what could be the anatomical site of lesion ?

Recurrent Focal seizures(secondary to CVA)

With Right hemiparesis

From Harrison principles of internal medicine.

After the focal seizure, the area of cortex that is most involved can have postictal depression of function lasting from minutes to hours. This can result in paralysis ("Todd paralysis") if the motor cortex is involved. Patients can have the appearance of focal deficit during this period and it may be difficult to distinguish from a patient with stroke. The history of seizure and the gradual recovery of function is critical to this differentiation.

If the focal seizure is not contained by normal inhibitory processes in the brain, it can spread to involve both hemispheres via the corpus callosum and/or the reticular formation of the mesodiencephalon and a generalized motor clinical seizure results. This may be tonic, tonic-clonic or just clonic in nature and is termed a "secondarily generalized seizure".

http://www.researchgate.net/publication/328562458_Approach_to_a_patient_with_monoplegia_and_hemiplegia

2. Why are subcortical internal capsular infarcts more common that cortical infarcts?

subcortical infarcts are caused by occlusion of a penetrating artery from a large cerebral artery, most commonly from the Circle of Willis. These penetrating arteries arise at sharp angles from major vessels and are thus, anatomically prone to constriction and occlusion.
So subcortical infarcts are more common than cortical infarcts.

http://casemed.case.edu/clerkships/neurology/NeurLrngObjectives/NeurLrngObj_Stroke01new.htm

https://www.ahajournals.org/doi/10.1161/01.STR.0000226993.88307.ff

https://www.frontiersin.org/articles/10.3389/fneur.2019.00860/full#B6

3. What is the pathogenesis involved in cerebral infarct related seizures?

https://images.app.goo.gl/nV59QZBaXKjHKTpP6

https://onlinelibrary.wiley.com/doi/abs/10.1111/epi.13965

MECHANISMS OF SEIZURE INITIATION AND PROPAGATION

Focal seizure activity can begin in a very discrete region of cortex and then slowly invade the surrounding regions. The hallmark of an established seizure is typically an electrographic “spike” due to intense near-simultaneous firing of a large number of local excitatory neurons, resulting in an apparent hypersynchronization of the excitatory bursts across a relatively large cortical region. The bursting activity in individual neurons (the “paroxysmal depolarization shift”) is caused by a relatively long-lasting depolarization of the neuronal membrane due to influx of extracellular calcium (Ca2+), which leads to the opening of voltage-dependent sodium (Na+) channels, influx of Na+, and generation of repetitive action potentials. This is followed by a hyperpolarizing after potential mediated by γ-aminobutyric acid (GABA) receptors or potassium (K+) channels, depending on the cell type. The synchronized bursts from a sufficient number of neurons result in a so-called spike discharge on the EEG. The spreading seizure wavefront is thought to slow and ultimately halt by intact hyperpolarization and a “surround” inhibition created by feedforward activation of inhibitory neurons. With sufficient activation, there is a recruitment of surrounding neurons via a number of synaptic and nonsynaptic mechanisms, including: (1) an increase in extracellular K+, which blunts hyperpolarization and depolarizes neighboring neurons; (2) accumulation of Ca2+ in presynaptic terminals, leading to enhanced neurotransmitter release; (3) depolarization-induced activation of the N-methyl-d-aspartate (NMDA) subtype of the excitatory amino acid receptor, which causes additional Ca2+ influx and neuronal activation; and (4) ephaptic interactions related to changes in tissue osmolarity and cell swelling. The recruitment of a sufficient number of neurons leads to the propagation of excitatory currents into contiguous areas via local cortical connections and to more distant areas via long commissural pathways such as the corpus callosum.

4. What is your take on the ecg?

And do you agree with the treating team on starting the patient on Enoxaparin?

https://www.aafp.org/afp/2009/0401/p560.html

5. Which AED would you prefer?

If so why?

Please provide studies on efficacies of each of the treatment given to this patient.

leviteracetam

https://pubmed.ncbi.nlm.nih.gov/10908898/

Of 294 patients randomized, 268 completed the study. Partial seizure frequency during the entire evaluation period (primary efficacy variable) was lower with levetiracetam compared to placebo (p /=10%), mostly mild to moderate in severity, with incidences higher than placebo were asthenia, dizziness, flu syndrome, headache, infection, rhinitis, and somnolence.

Conclusion: Adjunctive therapy with levetiracetam was effective and well tolerated in controlling partial seizures.

carbamazepine vs sodium valproate for partial seizures and secondary generalisation

https://pubmed.ncbi.nlm.nih.gov/1298221/

For the control of secondarily generalized tonic-clonic seizures, carbamazepine and valproate were comparably effective (in 136 patients and 138 patients, respectively). For complex partial seizures, four of five outcome measures favored carbamazepine (100 patients) over valproate (106 patients): the total number of seizures (2.7 vs. 7.6, P = 0.05), the number of seizures per month (0.9 vs. 2.2, P = 0.01), the time to the first seizure (P less than 0.02), and the seizure-rating score (P = 0.04). Carbamazepine was also superior according to a composite score that combined scores for the control of seizures and for adverse effects (P less than 0.001). Valproate was associated more frequently than carbamazepine with a weight gain of more than 5.5 kg (12 lb) (20 percent vs. 8 percent, P less than 0.001), with hair loss or change in texture (12 percent vs. 6 percent, P = 0.02), and with tremor (45 percent vs. 22 percent, P less than 0.001). Rash was more often associated with carbamazepine (11 percent vs. 1 percent, P less than 0.001).

Question 2) 55 year old man with Recurrent hypoglycemia

http://manojkumar1008.blogspot.com/2020/12/shortness-of-breath-with-high-sugars.html

Questions:

1. What is the problem representation for this patient?

Recurrent hypoglycemia secondary to OHAs with morbid obese k/c/o DM2 and HTN since 10 yrs with metabolic syndrome

sob since three days progresseive

symptoms of hypoglycemia refractory to dextrose infusion for 2 days

secondary to aki ?renal -acute tubular necrosis (non oliguric)

cough

2. What is the cause for his recurrent hypoglycemia? And how would you evaluate?

From Harrison principles of internal medicine

cause for recurrent hypoglycemia is drugs oha (glimiperide 1mg)

creatinine clearance 33ml/min

egfr is 26.2ml/min/1.73m2

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4732385/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4470208/

Sulfonylureas. Hypoglycemia risk is increased as a consequence of accumulation of the sulfonylurea and/or its active metabolites and their long duration of action [74]. Glibenclamide (glyburide) and its two active metabolites (M1 and M2) are cleared by the kidneys. Its use is not recommended for people with eGFRs < 60 mL/min/1.73 m2 [65,69,70]. Glimepiride and gliclazide can be used with caution in people with mild-moderate renal insufficiency, and dose reduction is usually necessary especially when eGFR is <30 mL/min/1.73 m2; however, it is recommended to consider alternative agents in people with moderate-severe renal insufficiency specifically when eGFR is <15 mL/min/1.73

evaluating the kidney function

renal function test-urea creatinine

ultrasound-size of the kidneys and rpd changes

cue-albuminuria

24hour urinary protein-quantification of proteinuria

gylcemic control:

fbs,plbs,hba1c

3. What is the cause for his Dyspnea? What is the reason for his albumin loss?

reason for albumin loss

spot urine protein creat ratio >1 , albuminuria

?diabetic nephropathy

https://www.aafp.org/afp/2000/0915/p1333.html

Pic

Approach to proteinuria from the above link.

4. What is the pathogenesis involved in hypoglycemia ?

From Harrison principles of internal medicine.

5) Do you agree with the treating team on

starting the patient on antibiotics? And why? Mention the efficacies for the treatment given.

I will not agree with the treating team on

starting the patient on antibiotics because of no proper indication and no rationale for antibiotics.

Q. 3

A. 41 year old man with Polyarthralgia

Case details here: https://mahathireddybandari.blogspot.com/2020/11/41m-with-chest-pain-and-joint-pains.html?m=1

1. How would you evaluate further this patient with Polyarthralgia?

Arthralgias should be differentiated from arthritis. Arthralgias are joint pains without obvious inflammation; whereas, arthritis is associated with demonstrable features of inflammation like joint swelling and tenderness. Raised temperature and visible redness are usually not seen in chronic arthritides like rheumatoid arthritis (RA) or spondarthritides (SpA). These are more a feature of conditions like acute gout or septic arthritis. Arthralgias are non-specific and seen in several non-MSK conditions, e.g. haematological diseases, post-viral fever, metabolic arthropathy like hypothyroidism, etc. A drug history may be important because some commonly used drugs like statins can cause MSK symptoms. Nature of Disease (Inflammatory or Non-Inflammatory?) One of the fundamental concepts in rheumatology is to differentiate inflammatory rheumatic diseases like RA, SpA, lupus, etc. from non-inflammatory disorders like osteoarthritis (OA) since the management is radically different. Inflamed joints stiffen or ‘gel’ after periods of inactivity and tend to loosen with use. In contrast, non-inflammatory or mechanical joint pain improves with rest and is typically associated with use related pain. Table 2 outlines the points that help in clinical differentiation. It has to be borne in mind that even patients with inflammatory joint disease can develop mechanical symptoms, for example, secondary OA of knees in a patient with RA.

UPPER LIMB VERSUS LOWER LIMB JOINT INVOLVEMENT

This can provide a clue to the differential diagnosis. Joints of both upper and lower limbs are involved in RA, SLE and psoriasis. Predominant involvement of lower limbs is seen in gout, SpA and erythema nodosum, whereas, haemochromatosis preferentially affects joints of upper limbs. Type of Joints Affected Small versus large RA typically affects both small and large joints. In fact, inflammatory, symmetric polyarthritis of small joints of hands like MCP joints and proximal interphalangeal (PIP) joints, is a characteristic feature of RA. Similarly, psoriasis, lupus and SSc affect both small and large joints. In contrast, SpA affects large joints much more than smaller joints. Therefore, the typical pattern of joint involvement in SpA is asymmetric oligoarthritis of large joints of lower limbs. Thus, the pattern in RA and SpA is quite different and distinctive, permitting bedside recognition. Specific joints These can give a clue to the nature of arthritic illness, e.g. distal interphalangeal (DIP) joint involvement is characteristic of OA, while DIP joints are spared in RA. Other conditions which give rise to DIP joint involvement are psoriasis and SSc. Involvement

of the first carpometacarpal joint is typical of OA, while ankle and shoulder are rarely involved in primary OA. Spine Spinal involvement other than cervical spine is rare in RA. In contrast, inflammatory low back pain is a characteristic feature of SpA. Sequence or Pattern of Involvement The three common patterns of joint involvement are intermittent, additive, and migratory. Intermittent arthritis is episodic and the patient may be totally asymptomatic in between the episodes. Examples include gout, Behçet’s syndrome, Reiter’s syndrome, intermittent hydrarthrosis, and palindromic rheumatism. Additive arthritis is one where more and more joints are afflicted with time. This is seen with RA, SpA, psoriasis, OA, etc. Migratory polyarthritis refers to a pattern wherein pain and swelling in a specific joint starts rapidly and subsides in 24 to 36 hours; the arthritis then picks up new joints. The difference from additive pattern is that the previously involved joints in migratory pattern return to normal as new joints become involved, whereas in the former the joint involvement persists. Migratory pattern is seen in rheumatic fever, gonococcal arthritis, viral disease, sarcoidosis, and bacterial endocarditis. These patterns may not be seen in the classical form due to treatment received by the patient. Also, these patterns may coexist in the same patient. However, when one pattern dominates, it may suggest a particular diagnosis. One of the commonly overlooked diagnoses in India is juvenile idiopathic arthritis (JIA), formerly known as juvenile rheumatoid arthritis (JRA) or juvenile chronic arthritis (JCA), in children below the age of 16 years. There is a tendency to label all joint pains in children as rheumatic fever (RF) with undue reliance on one laboratory marker, that is, elevated ASO (anti-streptolysin O) titres. The joint pains in RF are migratory, affect large joints and tend to subside over 6-12 weeks, with or without treatment. The major brunt is borne by the heart. In contrast, the arthritis in JIA tends to be additive, persistent, and may involve small or large joints. The presence of deformities strongly militates against a diagnosis of RF, since the arthritis in RF is most often non-deforming.

2. What is the pathogenesis involved in RA?

From Harrison principles of internal medicine.

PATHOGENESIS Thepathogenicmechanismsofsynovialinflammationarelikelyto resultfromacomplexinterplayofgenetic,environmental,andimmunologicfactorsthatproducesdysregulationoftheimmunesystemand abreakdowninself-tolerance(Fig. 351-4).Preciselywhattriggersthese initiatingeventsandwhatgeneticandenvironmentalfactorsdisrupt theimmunesystemremainsamystery.However,adetailedmolecular pictureisemergingofthemechanismsunderlyingthechronicinflammatoryresponseandthedestructionofthearticularcartilageandbone. InRA,thepreclinicalstageappearstobecharacterizedbyabreakdowninself-tolerance.Thisideaissupportedbythefindingthatautoantibodies,suchasRFandanti-CCPantibodies,maybefoundinsera frompatientsmanyyearsbeforeonsetofclinicaldisease.However, theantigenictargetsofanti-CCPantibodiesandRFarenotrestricted tothejoint,andtheirroleindiseasepathogenesisremainsspeculative. Anti-CCPantibodiesaredirectedagainstdeaminatedpeptides,which resultfromposttranslationalmodificationbytheenzymePADI4.They recognizecitrulline-containingregionsofseveraldifferentmatrixproteins,includingfilaggrin,keratin,fibrinogen,andvimentin,andare presentathigherlevelsinthejointfluidcomparedtotheserum.Other autoantibodieshavebeenfoundinaminorityofpatientswithRA, buttheyalsooccurinthesettingofothertypesofarthritis.Theybind toadiversearrayofautoantigens,includingtypeIIcollagen,human cartilagegp-39,aggrecan,calpastatin,immunoglobulinbindingprotein (BiP),andglucose-6-phosphateisomerase.

3. What are the treatment regimens for a patient with RA and their efficacies?

DMARDsaresonamedbecauseoftheirabilitytosloworprevent structuralprogressionofRA.TheconventionalDMARDsinclude hydroxychloroquine,sulfasalazine,methotrexate,andleflunomide; theyexhibitadelayedonsetofactionof~6–12weeks.Methotrexate istheDMARDofchoiceforthetreatmentofRAandistheanchor drugformostcombinationtherapies.ItwasapprovedforthetreatmentofRAin1988andremainsthebenchmarkfortheefficacyand safetyofnewdisease-modifyingtherapies.Atthedosagesused forthetreatmentofRA,methotrexatehasbeenshowntostimulate adenosinereleasefromcells,producingananti-inflammatoryeffect. Theclinicalefficacyofleflunomide,aninhibitorofpyrimidinesynthesis,appearssimilartothatofmethotrexate;ithasbeenshownin well-designedtrialstobeeffectiveforthetreatmentofRAasmonotherapyorincombinationwithmethotrexateandotherDMARDs. AlthoughsimilartotheotherDMARDsinitsslowonsetof action,hydroxychloroquinehasnotbeenshowntodelayradiographicprogressionofdiseaseandthusisnotconsideredtobea trueDMARD.Inclinicalpractice,hydroxychloroquineisgenerally usedfortreatmentofearly,milddiseaseorasadjunctivetherapyin combinationwithotherDMARDs.Sulfasalazineisusedinasimilar mannerandhasbeenshowninrandomized,controlledtrialsto reduceradiographicprogressionofdisease.Minocycline,goldsalts, penicillamine,azathioprine,andcyclosporinehaveallbeenusedfor thetreatmentofRAwithvaryingdegreesofsuccess;however,they areusedsparinglynowduetotheirinconsistentclinicalefficacyor unfavorabletoxicityprofile. BIOLOGICALS BiologicDMARDshaverevolutionizedthetreatmentofRAoverthe pastdecade(Table351-2).Theyareproteintherapeuticsdesigned mostlytotargetcytokinesandcell-surfacemolecules.TheTNF inhibitorswerethefirstbiologicalsapprovedforthetreatmentof RA.Anakinra,anIL-1receptorantagonist,wasapprovedshortly thereafter;however,itsbenefitshaveprovedtoberelativelymodest comparedwiththeotherbiologicalsandthereforethisbiological israrelyusedforthetreatmentofRAwiththeavailabilityofother moreeffectiveagents.Abatacept,rituximab,andtocilizumabarethe newestmembersofthisclass. Anti-TNF Agents ThedevelopmentofTNFinhibitorswasoriginally spurredbytheexperimentalfindingthatTNFisacriticalupstream mediatorofjointinflammation.Currently,fiveagentsthatinhibit TNF-αareapprovedforthetreatmentofRA.Therearethreedifferentanti-TNFmonoclonalantibodies.Infliximabisachimeric(part mouseandhuman)monoclonalantibody,whereasadalimumaband golimumabarehumanizedmonoclonalantibodies.Certolizumab pegolisapegylatedFc-freefragmentofahumanizedmonoclonal antibodywithbindingspecificityforTNF-α.Lastly,etanerceptisa solublefusionproteincomprisingtheTNFreceptor2incovalent linkagewiththeFcportionofIgG1.AlloftheTNFinhibitorshave beenshowninrandomizedcontrolledclinicaltrialstoreducethe signsandsymptomsofRA,slowradiographicprogressionofjoint damage,andimprovephysicalfunctionandqualityoflife.AntiTNFdrugsaretypicallyusedincombinationwithbackground methotrexatetherapy.Thiscombinationregimen,whichaffords maximalbenefitinmanycases,isoftenthenextstepfortreatment ofpatientswithaninadequateresponsetomethotrexatetherapy. Etanercept,adalimumab,certolizumabpegol,andgolimumabhave alsobeenapprovedforuseasmonotherapy. Anti-TNFagentsshouldbeavoidedinpatientswithactiveinfectionorahistoryofhypersensitivitytotheseagentsandarecontraindicatedinpatientswithchronichepatitisBinfectionorclassIII/IV congestiveheartfailure.Themajorconcernistheincreasedriskfor infection,includingseriousbacterialinfections,opportunisticfungal infection,andreactivationoflatenttuberculosis.Forthisreason,all patientsarescreenedforlatenttuberculosisaccordingtonational guidelinespriortostartinganti-TNFtherapy(Chap. 173).Inthe UnitedStates,patientsareskin-testedusinganintradermalinjection ofpurifiedproteinderivative(PPD);individualswithskinreactions of>5mmarepresumedtohavehadpreviousexposuretotuberculosisandareevaluatedforactivediseaseandtreatedaccordingly.Use ofanIFN-γreleaseassaymayalsobeappropriateforscreeningas somedatasuggestalowerrateoffalse-negativeandfalse-positive testswithanIFN-γreleaseassaycomparedtoskintestingwithPPD inpatientstreatedwithcorticosteroids.WhileacombinationofPPD skintestandIFN-γreleaseassaymayofferthehighestsensitivityfor screeningpurposes,noconsensusguidelinesexist. Anakinra AnakinraistherecombinantformofthenaturallyoccurringIL-1receptorantagonist.Althoughanakinrahasseenlimited useforthetreatmentofRA,ithasenjoyedaresurgenceoflateas aneffectivetherapyofsomerareinheritedsyndromesdependent onIL-1production,includingneonatal-onsetinflammatorydisease, Muckle-Wellssyndrome,andfamilialcoldurticaria,aswellassystemicjuvenile-onsetinflammatoryarthritisandadult-onsetStill’s disease.Anakinrashouldnotbecombinedwithananti-TNFdrug duetothehighrateofseriousinfectionsobservedwiththisregimen inaclinicaltrial. Abatacept Abataceptisasolublefusionproteinconsistingofthe extracellulardomainofhumanCTLA-4linkedtothemodifiedportionofhumanIgG.Itinhibitstheco-stimulationofTcellsbyblockingCD28-CD80/86interactionsandmayalsoinhibitthefunction ofantigen-presentingcellsbyreversesignalingthroughCD80and CD86.Abatacepthasbeenshowninclinicaltrialstoreducedisease activity,slowradiographicprogressionofdamage,andimprove functionaldisability.ManypatientsreceiveabataceptincombinationwithmethotrexateoranotherDMARDsuchasleflunomide. Abatacepttherapyhasbeenassociatedwithanincreasedriskof infection. Rituximab Rituximabisachimericmonoclonalantibodydirected againstCD20,acell-surfacemoleculeexpressedbymostmatureB lymphocytes.ItworksbydepletingBcells,whichinturn,leadstoa reductionintheinflammatoryresponsebyunknownmechanisms. Thesemechanismsmayincludeareductioninautoantibodies, inhibitionofTcellactivation,andalterationofcytokineproduction. RituximabhasbeenapprovedforthetreatmentofrefractoryRA incombinationwithmethotrexateandhasbeenshowntobemore effectiveforpatientswithseropositivethanseronegativedisease. Rituximabtherapyhasbeenassociatedwithmildtomoderate infusionreactionsaswellasanincreasedriskofinfection.Notably, therehavebeenrareisolatedreportsofapotentiallylethalbrain disorder,progressivemultifocalleukoencephalopathy(PML),in associationwithrituximabtherapy,althoughtheabsoluteriskof thiscomplicationappearstobeverylowinpatientswithRA.Most ofthesecaseshaveoccurredonabackgroundofpreviousorcurrent exposuretootherpotentimmunosuppressivedrugs. Tocilizumab Tocilizumabisahumanizedmonoclonalantibody directedagainstthemembraneandsolubleformsoftheIL-6 receptor.IL-6isaproinflammatorycytokineimplicatedinthe pathogenesisofRA,witheffectsonbothjointinflammationand damage.IL-6bindingtoitsreceptoractivatesintracellularsignaling pathwaysthataffecttheacute-phaseresponse,cytokineproduction, andosteoclastactivation.Clinicaltrialsattesttotheclinicalefficacy oftocilizumabtherapyforRA,bothasmonotherapyandincombinationwithmethotrexateandotherDMARDs.Tocilizumab has beenassociatedwithanincreasedriskofinfection,neutropenia, andthrombocytopenia;thehematologicabnormalitiesappeartobe reversibleuponstoppingthedrug.Inaddition,thisagenthasbeen showntoincreaseLDLcholesterol.However,itisnotknownasyet ifthiseffectonlipidlevelsincreasestheriskfordevelopmentof atheroscleroticdisease.

3) (B)

75 year old woman with post operative hepatitis following blood transfusion

Case details here: https://bandaru17jyothsna.blogspot.com/2020/11/this-is-online-e-log-book-to-discuss.html

1.What are your differentials for this patient and how would you evaluate?

https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/delayed-hemolytic-transfusion-reaction

Delayed hemolytic transfusion reactions (DHTRs) occur 3–10 days after the transfusion of RBC products that appear to be serologically compatible. These reactions occur in patients who have been alloimmunized to minor RBC antigens during previous transfusions and/or pregnancies; pretransfusion testing fails to detect these alloantibodies due to their low titer. After reexposure to antigen-positive RBCs, an anamnestic response occurs, with a rapid rise in antibody titer. Decreased survival of the transfused RBCs may result, primarily due to extravascular hemolysis. In the majority of cases, however, anamnestic antibody production does not cause detectable hemolysis. The term delayed serologic transfusion reaction (DSTR) defines reactions in which an anamnestic antibody is identified serologically, in the absence of clinical evidence of accelerated RBC destruction. Antigens implicated most often in DHTRs and DSTRs are in the Kidd, Duffy, Kell, and MNS systems, in order of decreasing frequency.

2. What would be your treatment approach? Do you agree with the treatment provided by the treating team and why? What are their efficacies?

Treatment is only supportive management with no role of udiliv as the cause for hepatitis is self resolving with increased about of bilirubin due to destruction of rbc as substrate for hepatitis.

https://www.ijbcp.com/index.php/ijbcp/article/view/64

Background: Data on clinical spectrum and etiology of chronic cholestatic liver disease (CCLD) in Indian patients is limited. This prospective, observational real-world study aimed to profile patients with CCLD being recommended Udiliv®, determine reasons for recommendation along with its safety and effectiveness.

Methods: CCLD patients (18-65 years) scheduled to receive Udiliv® as part of routine clinical practice were enrolled. Healthcare utilizations, clinical manifestations (jaundice, pruritus, fatigue) and liver biochemistry were assessed over 12 weeks. Reasons for recommending Udiliv® were recorded at the initiation of therapy.

Results: The intent-to-treat analysis population included 248 patients. The mean (±SD) age was 44.1(11.8) years and 78.23% were males. Majority (89.1%) were classified as intrahepatic cholestasis (IHC). Most common etiologies of IHC were alcoholic liver disease (ALD) (39.92%) and viral hepatitis (24.60%) followed by non-alcoholic fatty liver disease (NAFLD) (22.18%), which is less well known. Udiliv®, 300 mg twice daily was preferred dose due to known efficacy (73.39%), as standard of care (62.5%) and good tolerability (45.56%). There was reduction in healthcare visits, inpatient hospitalization and days off work, within 4 weeks of treatment initiation (P<0.0001). There was improvement in clinical presentation (P<0.0001) and reduction in biochemical markers over 12 weeks. The treatment was well-tolerated.

Q.4) 60 year woman with Uncontrolled sugars

http://manojkumar1008.blogspot.com/2020/12/60-yr-old-female-with-uncontrolled.html

1. What is the problem representation of this patient?

chest pain -radiating to epigastrium and back

uncontrolled sugars

leucocytosis secondary to ?community acquired pneumonia

?lung abscess

no further history mentioned in terms of fever , cough, sob

2. What are the factors contributing to her uncontrolled blood sugars?

Reason for uncontrolled sugars

sepsis

poor glycemic control prior to hospital administration with hba1c 8, (history not clear about compliance)

https://www.semanticscholar.org/paper/Stress-hyperglycemia%2C-insulin-and-immunomodulation-Marik-Raghavan/24f1499f7360fc0564d7f66cee5cfa7953c73616

Changes in whole-body glucose uptake and glucose oxidation in sepsis are complex and may depend on the severity of illness and the stage of the disease. Wholebody glucose uptake and glucose oxidation may be increased in the early stages of sepsis and endotoxemia [25, 26]. This may be the result of cytokine-induced increase in non-insulin mediated glucose uptake by tissues rich in mononuclear phagocytes, including the liver, spleen, ileum, and lung [27, 28]. Enhanced noninsulin mediated glucose uptake appears to result from an increase in the synthesis, concentration or activity of the GLUT1 transporter [29, 30]. With the development of insulin resistance glucose utilization and oxidation may decrease [25, 31, 32]. Exogenous insulin increases glucose utilization and oxidation; however, nonoxidative disposal (storage) remains impaired [25, 31

3. What are the chest xray findings?

The xray findings in this pt are

p/a view ,adequate exposure with opacities in right upper lobe ,

with air bronchogram, with bulging fissure sign suggestive of lobar consolidation

4. What do you think is the cause for her hypoalbuminaemia? How would you approach it?

hypoalbunemia

https://www.dvm360.com/view/approach-hypoalbuminemia-proceedings

The potential causes of hypoalbuminemia are many, and include:

Hepatic failure (failure of albumin synthesis)

Gastrointestinal protein loss (protein-losing enteropathy)

Renal protein loss (protein-losing nephropathies)

Other external losses in exudate or hemorrhage

Hyperglobulinemia (with a 'compensatory' decrease in albumin production)

Starvation/protein malnutrition

Chronic illness

Hypoadrenocorticism

Laboratory error

the cause in this patient can be attributes to malnutrition or albumin as acute phase reactant

https://onlinelibrary.wiley.com/doi/10.1002/jpen.1451

Inflammation increases capillary permeability and escape of serum albumin, leading to expansion of interstitial space and increasing the distribution volume of albumin. The half‐life of albumin has been shown to shorten, decreasing total albumin mass. These 2 factors lead to hypoalbuminemia despite increased fractional synthesis rates in plasma.

5. Comment on the treatment given along with each of their efficacies with supportive evidence.

treatment efficacies

piperacillin tazobactum

https://pubmed.ncbi.nlm.nih.gov/9721959/

A favorable clinical response was observed in 90% of the piperacillin/ tazobactam group and in 84% of the co-amoxiclav/aminoglycoside group (not significant). The bacteriological efficacy was comparable in both groups

clarithromycin

https://journal.chestnet.org/article/S0012-3692(15)42279-2/abstract

This randomized, double-blind multicenter study compared clarithromycin and cefixime as treatment for patients with community-acquired lower respiratory tract infections (n=213). Patients had bacterial pneumonia (clarithromycin, 19 percent; cefixime, 21 percent) or acute bacterial exacerbation of chronic bronchitis or asthmatic bronchitis (clarithromycin, 81 percent; cefixime, 79 percent). Patients received 500 mg of clarithromycin twice daily (n = 103) or 400 mg of cefixime once daily (n = 110) for 7 to 14 days.

Clinical cure or improvement occurred in 86 percent of the clarithromycin-treated patients and 88 percent of the cefixime-treated patients.

Q.5) 56 year old man with Decompensated liver disease

Case report here: https://appalaaishwaryareddy.blogspot.com/2020/11/56year-old-male-with-decompensated.html

1. What is the anatomical and pathological localization of the problem?

Anatomical and pathological localisation

as per the symptoms

jaundice with abdominal distention-liver

sob with abdominal distention-heart failure, renal failure

examination- ecchymosis and petechiae-bleeding manifestations in uraemia, ?liver failure(no reports of coagulation profile)

chronic mild elevations with AST>ALT (2:1) are suggestive of alcohol related liver injury or cirrhosiscompared to the chronic viral hepatitis due to hepatitis B.

Hepatorenal failure type 1 , with increase in serum creatinine

liver by sheila page 140

2. How do you approach and evaluate this patient with Hepatitis B?

Patients with chronic hepatitis B (CHB) are diagnosed when hepatitis B surface antigen (HBsAg) persists in serum for more than 6 months. There are two main forms of chronic hepatitis B: (a) HBeAg-positive form associated with wild-type infection; and (b) HBeAg negative form associated with core promoter and/ or pre-core mutant viruses. Hepatitis B core antibody (Total) is present in CHB infection and presence of HBeAg or high HBV-DNA are markers of replicative virus. The transaminases (AST, ALT) are typically elevated usually 1 to 5 times the upper limit of normal with ALT> AST, whereas the alkaline phosphatase level is only mildly elevated. The albumin: globulin ratio remains normal except in advanced stages of disease where reversal of A:G ratio may be seen. Abdominal ultrasonography (USG) is the most commonly used imaging modality although it is not useful in making the diagnosis. Its importance, however, lies in distinguishing patients with cirrhosis (small, shrunken nodular liver or atrophy of right lobe with hypertrophy of caudate/left lobe) or those with portal hypertension.

3. What is the pathogenesis of the illness due to Hepatitis B?

The typical morphologic lesions of all types of viral hepatitis are similar and consist of panlobular infiltration with mononuclear cells, hepatic cell necrosis, hyperplasia of Kupffer cells, and variable degrees of cholestasis. Hepatic cell regeneration is present, as evidenced by numerous mitotic figures, multinucleated cells, and “rosette” or “pseudoacinar” formation. The mononuclear infiltration consists primarily of small lymphocytes, although plasma cells and eosinophils occasionally are present. Liver cell damage consists of hepatic cell degeneration and necrosis, cell dropout, ballooning of cells, and acidophilic degeneration of hepatocytes (forming so-called Councilman or apoptotic bodies). Large hepatocytes with a ground-glass appearance of the cytoplasm may be seen in chronic but not in acute HBV infection; these cells contain HBsAg and can be identified histochemically with orcein or aldehyde fuchsin. In uncomplicated viral hepatitis, the reticulin framework is preserved.

4. Is it necessary to have a separate haemodialysis set up for hepatits B patients and why?

It could remain viable for at least 7 days on environmental surfaces at room temperature.[12] Being a blood handling procedure, hemodialysis, therefore, poses an exceptional risk to dialysis patients as well as clinical staff in terms of nosocomial transmission of HBV. The patients could acquire the infection through injections of contaminated material, having mucosal membrane or breached skin exposed to infective material or being dialyzed with contaminated equipment

HBV DNA had been detected even in the dialysate and ultrafiltrate of those HBsAg positive undergoing high-flux hemodialysis,

There should be no sharing of supplies, vials, medications, instruments and even ancillary items such as clamps, scissors, blood pressure cuffs and other non-disposable items. Previous studies, indeed, showed that non-separation of infected from non-infected patients was associated with an increased risk of infection while segregation has been shown to be effective

Therefore as per this study, the patients are segregated due to the shortcomings of proper maintenance in our setup

https://www.hepatitisbannual.org/article.asp?issn=0972-9747;year=2006;volume=3;issue=1;spage=76;epage=105;aulast=Wong

https://www.cdc.gov/mmwr/preview/mmwrhtml/rr5005a1.htm

5. What are the efficacies of each treatment given to this patient? Describe the efficacies with supportive RCT evidence.

efficacy of tenofovir

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5220271/#:~:text=Among%20HBeAg%2Dpositive%20patients%2C%20rates,na%C3%AFve%20and%20treatment%2Dexperienced%20patients.

Ninety-two patients were identified who fulfilled the enrolment criteria. Median follow-up was 26 mo (range 3-114). Mean age was 46 (24-78) years, 64 (70%) were male and 77 (84%) were of Asian origin. 55 (60%) patients were treatment-naïve and 62 patients (67%) were HBeAg-negative. Complete virological suppression was achieved by 45/65 (71%) patients at 12 mo, 37/46 (80%) at 24 mo and 25/28 (89%) at 36 mo. Partial virological response (HBV DNA 20-2000 IU/mL) was achieved by 89/92 (96.7%) of patients. Multivariate analysis showed a significant relationship between virological suppression at end of follow-up and baseline HBV DNA level (OR = 0.897, 95%CI: 0.833-0.967, P = 0.0046) and HBeAg positive status (OR = 0.373, 95%CI: 0.183-0.762, P = 0.0069

aldactone

https://pubmed.ncbi.nlm.nih.gov/6339312/#:~:text=These%20results%20indicate%20that%20(a,and%20spironolactone%20in%20these%20patients

Group 1 contained 21 patients treated with furosemide; group 2 contained 19 patients treated with spironolactone. The initial doses were 80 and 150 mg/day, respectively. These doses were increased to 160 and 300 mg/day, respectively, if there was no response. Cases not responding to furosemide and spironolactone were later treated with spironolactone and furosemide, respectively. In group 1, 11 of the 21 patients responded to furosemide, while in group 2, 18 of the 19 patients responded to spironolactone (p less than 0.01).

6) 58 year old man with Dementia

Case report details: http://jabeenahmed300.blogspot.com/2020/12/this-is-online-e-log-book-to-discuss.html

1. What is the problem representation of this patient?

Current problem: forgetfulness since 3 months impairing his daily activities as well

Deviation of mouth ,leading to slurring of speech and unable to swallow since one month which increased

Altered sensorium (delirium) with intact awareness , fluctuations

Slurring of speech since 6 months , deviation of mouth to right side associated with

Drooling of saliva from left angle of mouth, food particles and water predominantly from left angle of mouth and smacking of lips

Urinary incontinence since 6 months, dribbling of urine while rushing to bathroom.

Forgetfulness since 3 months

2. How would you evaluate further this patient with Dementia?

Three major issues should be kept at the forefront: (1) What is the best fit for a clinical diagnosis? (2) What component of the demen-tia syndrome is treatable or reversible? (3) Can the physician help to alleviate the burden on caregivers? A broad overview of the approach to dementia is shown in Table 25-3. The major degenera-tive dementias can usually be distinguished by the initial symptoms; neuropsychological, neuropsychiatric, and neurologic findings; and neuroimaging features (Table 25-4).

PHYSICAL AND NEUROLOGIC EXAMINATIONA thorough general and neurologic examination is essential to doc-ument dementia, to look for other signs of nervous system involve-ment, and to search for clues suggesting a systemic disease that might be responsible for the cognitive disorder. Typical AD spares motor systems until later in the course. In contrast, FTD patients often develop axial rigidity, supranuclear gaze palsy, or a motor neuron disease reminiscent of amyotrophic lateral sclerosis (ALS). In DLB, the initial symptoms may include the new onset of a parkin-sonian syndrome (resting tremor, cogwheel rigidity, bradykinesia, festinating gait), but DLB often starts with visual hallucinations or dementia. Symptoms referable to the lower brainstem (RBD, gastro-intestinal or autonomic problems) may arise years or even decades before parkinsonism or dementia. Corticobasal syndrome (CBS) features asymmetric akinesia and rigidity, dystonia, myoclonus, alien limb phenomena, pyramidal signs, and prefrontal deficits such as nonfluent aphasia with or without motor speech impairment, executive dysfunction, apraxia, or a behavioral disorder. Progressive supranuclear palsy (PSP) is associated with unexplained falls, axial rigidity, dysphagia, and vertical gaze deficits. CJD is suggested by the presence of diffuse rigidity, an akinetic-mute state, and promi-nent, often startle-sensitive myoclonus.

3. Do you think his dementia could be explained by chronic infarcts?

Other concurrent factors, which are not yet fully understood, could be hypothesized as follows: a decrease of blood flow in the white matter of normal elderly subjects,27 the decrease possibly enhanced in patients with vascular risk factors; so-called incomplete white matter infarcts30; the occurrence of subsequent lacunar or large infarcts; the site of the lesion, perhaps of more relevance than its volume1831-34; the degree of cerebral atrophy18; and corticosubcortical disconnections in thalamo- and striato-cortical pathways.

https://documentcloud.adobe.com/link/review?uri=urn:aaid:scds:US:e999cbad-a49f-4d17-ae4d-7b64e30a99e7

4. What is the likely pathogenesis of this patient's dementia?

Pathophysiology depends on the type of dementia presentation as stated below.

(

https://www.researchgate.net/publication/333733171_Dementia_prevalence_and_pathophysiology

The gross pathologic hallmark of FTLD is a focal atrophy of frontal, insular, and/or temporal cortex, which can be visualized with neuroimaging studies (Fig. 424-1) and is often profound at autopsy. Despite the appearance of advanced disease, however, imaging studies suggest that atrophy often begins focally in one hemisphere before spreading to anatomically interconnected cortical and subcortical regions. Loss of cortical serotonergic innervation is seen in many patients. In contrast to AD, the cholinergic system is relatively spared in FTD, which accounts for the poor efficacy of acetylcholinesterase inhibitors in this group. Although early studies suggested that 15–30% of patients with FTD showed underlying AD at autopsy, progressive refinement in clinical diagnosis has improved pathologic prediction accuracy, and most patients diagnosed with FTD at a dementia clinic with expertise in FTD will show underlying FTLD pathology. Microscopic findings seen across all patients with FTLD include gliosis, microvacuolation, and neuronal loss, but the disease is subtyped according to the protein composition of neuronal and glial inclusions, which contain either tau or TDP-43 in ~90% of patients, with the remaining ~10% showing inclusions containing FUS

5. Are you aware of pharmacological and non pharmacological interventions to treat such a patient and what are their known efficacies based on RCT evidence?

PHARMACOLOGIC:

Cholinesterase inhibitors:

Donepezil

Rivastigmine

Galantamine

NMDA antagonist:

Memantine

NON PHARMACOLOGIC:

Counselling the patient and care givers

Geriatric care

Cognitive / emotion oriented interventions

Sensory stimulation interventions

Behaviour management techniques

https://pubmed.ncbi.nlm.nih.gov/9443470/

Q. 7) 22 year old man with seizures

Case report here http://geethagugloth.blogspot.com/2020/12/a-22-year-old-with-seizures.html

1. What is the problem representation of this patient ? What is the anatomic and pathologic localization in view of the clinical and radiological findings?

A 22 year old delivery boy chronic alcoholic and tobacco chewer c/o on & off fever since 1 year , involuntary weight loss since 6 months , headache since 2 months , 4 - 5 episodes of involuntary stiffening of both UL & LL with 5 min LOC 1 week before the day of admission.

Brain - multiple ring enhancing lesions in right cerebellum ? Tuberculoma

RVD positive

2. What the your differentials to his ring enhancing lesions?

Bacterial

Pyogenic abscess

Tuberculoma and tuberculous abscess Mycobacterium avium-intracellulare infection Syphilis

Listeriosis

Fungal

Nocardiosis

Actinoimycosis

Rhodococcosis

Zygomycosis

Histoplasmosis

Coccidioidomycosis

Aspergillosis

Mucormycosis

Paracoccidioidomycosis

Cryptococcosis

Parasitic

Neurocysticercosis

Toxoplasmosis

Amoebic brain abscess

Echinococcosis

Cerebral sparganosis

Chagas' disease

Neoplastic

Metastases

Primary brain tumor

Primary CNS lymphoma

Inflammatory and demyelinating

Multiple sclerosis

Acute disseminated encephalomyelitis

Sarcoidosis

Neuro-Behcet.s disease

Whipple's disease

Systemic lupus erythematosus

3. What is "immune reconstitution inflammatory syndrome IRIS and how was this patient's treatment modified to avoid the possibility of his developing it?

A paradoxical clinical worsening of a known condition or the appearance of a new condition after initiating anti retroviral therapy (ART) therapy in HIV-infected patients resulting from restored immunity to specific infectious or non-infectious antigens is defined as immune reconstitution inflammatory syndrome (IRIS).

since the cd4 count is above 300,

the patient is currently started on att for 6 months and then planned for art

Q 8) Please mention your individual learning experiences from this month.

Randomly walking across the casualty saw a case of toxicology which was treated by activated charcoal found interesting by listening sound from distant 1 gm /kg.

Imagining the number of tablets should be given.