January bimonthly assessment

1.26 year old woman with complaints of altered sensorium since 1 day,headache since 8 days,fever and vomitings since 4 days

More here: https://harikachindam7.blogspot.com/2020/12/26-year-old-female-with-complaints-of.html

Case presentation  links: 

https://youtu.be/fz9Jssoc-mA

https://youtu.be/d4lLX04oL8s

https://youtu.be/CSCxw2zp7Oc

a). What is the problem representation of this patient and what is the anatomical localization for her current problem based on the clinical findings?

26 yr old female who got evaluated for joint pains before and diagnosed as SLE with no other comorbities and is on immunosuppresants for SLE ,


Came with history of head ache since 8 days and fever plus vomitings , generalised weakness since 4 days and altered sensorium since one day.


So trigger point is Altered sensorium for which they came to hospital , which was intially thought to be due to 


1) Hyponatremia.


2) Euvolemic Hyponatremia ( as there was no signs of fluid overload or hypotension) secondary to SIADH - (SIADH secondary to TUBERCULAR MENINGITIS) .


3) TUBERCULAR MENINGITIS. ( CSF cbnaat came positive and also cell count revealed lymphocytosis,


with low glucose and chloride and increased CSF protein. - evident of tb meningitis.


4) ACUTE INFARCT IN LEFT THALAMUS .( secondary to vasculitis ) .


Stroke in TBM patients may develop insidiously and present as asymptomatic or silent stroke. The most common vulnerable brain region was basal ganglia where has been described as ‘tubercular zone’. It is comprised of head of the caudate nucleus, anteriomedial thalami and anterior limb and genu of internal capsule.


 In a study involving 122 TBM patients, 55 patients had stroke and 54% strokes were located in basal ganglia . Another study had similar results with 49% of infarctions in basal ganglia . 


In our study, 50% of patients had stroke located in basal ganglia, which is consistent with previous studies. Strokes in ‘tubercular zone’ may be associated with basilar exudates. 


Dense fibrinocellular exudates may wrap middle cerebral trunks and their penetrating branches, which may contribute to vasculitis and cause strokes in ‘tubercular zone’. 




Age, CSF white blood cell and basal meningeal enhancement can predict the occurrence of acute ischemic stroke in young adults with TBM.


Stroke in TBM patients was mainly caused by vasculitis secondary to the meningeal inflammation, which can be classified into three patterns: 1) infiltrative, 2) proliferative and 3) necrotizing vascular lesions . Duration of TBM may determine the relative frequency of infiltrative, proliferative and necrotizing changes in the cerebral vessels.


b) What is the etiology of the current problem and how would you as a member of the treating team arrive at a diagnosis? Please chart out the sequence of events timeline between the manifestations of each of her problems and current outcomes. 


Etiology:Tubercularmeningitis

Sequence of events:


2010: marriage

2011: 1st child birth (male)

2012: 2nd child birth (female)

2014: Both hands small joints pain progressed to elbow and shoulder - relieved with treatment @ local RMP

2017: Multiple joint pains - diagnosed as SLE & started on treatment

2020 (december): - headache on& off 1-2 times/week relieved with treatment

Increased headache from 15 days

10 days back stopped methyl prednisolone

 vomitings from 1 week

Fever, neckpain, generalized weakness & decreased appetite from 4 days

Admitted to a local hospital and @ night went to bathroom and fell down in a state of altered sensorium

Same day presented to our casualty @ around

3 am in a state of altered sensorium & irrelevant speech

C) What is the efficacy of each of the drugs listed in her prior treatment plan that she was following since last two years before she stopped it two weeks back? 


A) Pt was on medication for SLE (Hydrochloroquine-200mg/OD,Sulfasalazine,Methylprednisolone,Alandronic acid and Cholecalciferol,Aceclofenac,Flupirtine,Gabapentine,Methylcobalamin tablets), which she stopped 10 days bac




Methylprednisolone and Cyclophosphamide, Alone or in  Combination, in Patients with Lupus Nephrit


RANDOMISED CONTROL TRIAL


-Therapy for patients with life-threatening sys- temic lupus erythematosus has included high doses of corticosteroids and cytotoxic or cytostatic drugs . Cyclophosphamide, given in intermit- tent intravenous boluses, has been widely used to treat renal , and central nervous system disease , but this therapy is sometimes withheld in the hope that disease might be controlled with corticosteroids or other immuno- suppressive dru


P - 82 patients with lupus nephritis . To enter the  study, patients had to have both glomerulonephritis  and a diagnosis of systemic lupus erythematos


I - High dose methyl prednisolone (1g/m2 BSA) - Once A month for 1 y


C - Comparision with standard therapy with cyclophosphamide (0.5-1g/m2 BSA) for 6 months then quarterly o


Combination of cyclophosphamide and methyl prednisolon


O -The primary study outcome was the response to the study drugs as defined by 1) the percentage of patients who achieved renal remission, 2) the num- ber of nonresponders (nonresponse was defined as >10 erythrocytes per high-power field, cellular casts, proteinuria [>1 g of protein per day], and doubling of the serum creatinine level), and 3) the percent- age of adverse events


Secondary outcome measures were renal failure that required dialysis (end-stage renal disease), sta- ble doubling of the serum creatinine level, and number of renal relapses (renal relapse was defined as a reactivation of renal disease after 6 or more months of remission




Bisphosphonates for steroid induced osteoporosi


P - We chose studies where participants were men and/or women over the age of 18, with underlying inflammatory disorders, initiating treatment or currently being treated with systemic corticosteroids (primary or secondary prevention), and who had not received bis- phosphonates in the six months prior to the start of the study


Pri- mary prevention was defined by bisphosphonate treatment starting within three months of initiating corticosteroids. Due to con- troversy in the literature regarding low dose steroids and the risk of osteoporosis, only those trials where the mean corticosteroid dose was 7.5 mg/day or higher were use


I -Controlled clinical trials that included any of the first or second generation bisphosphonates, alone or in combination with cal- cium and/or vitamin D, with the control group taking placebo, alone or in combination with calcium and/or vitamin D were in- clude


O -The primary outcome assessed and required for inclusion in the meta-analysis was percent change in BMD at one year at the lum- bar spine or femoral neck. Data regarding number of new verte- bral fractures was collected if presen


Corticosteroids are widely used to treat inflammation. Bone loss (osteoporosis) is a serious side effect of this therapy. We reviewed a total of 13 trials which included 842 patients. We found that the bone mineral density of the lumbar spine of patients taking bisphosphonate therapy improved 4.3% more than patients who had no treatment. At the femoral neck (top of the thigh bone), the bone mineral density improved 2.1% more in the treatment group. There was no difference in the number of spinal fractures between the the two groups. We found that bisphosphonates are effective at preventing and treating corticosteroid-induced bone loss at the lumbar spine and femoral neck. We do not have enough evidence to say whether or not bisphosphonates prevent fracture


A total of 13 trials, including 842 patients are included in this meta-analysis. Results are reported as a weighted mean difference of the percent change in BMD between the treatment and placebo groups, with trials being weighted by the inverse of their varianc


 The 95% confidence intervals (95% CI) are presented. At the lumbar spine, the weighted mean difference of BMD between the treatment and placebo groups was 4.3% (95% CI 2.7, 5.9). At the femoral neck, the weighted mean difference was 2.1% (95%CI 0.01, 3.8). Although there was a 24% reduction in odds of spinal fractures [OR 0.76 (95%CI 0.37, 1.53)], this result was not statistically significant.e.s.t.d.d.. s : ).. e.r r.usg. :is: k.



d) Please share Any reports around similar patients with SLE and TB meningitis?


Here's a case report of a 31 year old woman diagnosed with SLE and subsequently developed SLE myocarditis and Lupus Nephritis who also developed TB meningitis


https://pubmed.ncbi.nlm.nih.gov/28764615/


Another case report of a 51 year old woman with SLE who later developed TB meningitis

https://pubmed.ncbi.nlm.nih.gov/10067053/


e) What is the sensitivity and specificity of ANA in the diagnosis of SLE? 


To determine the sensitivity and specificity of ANA and anti-dsDNA in SLE patients, using sera from Healthy controls and Multiple Medical problem patients.

The prevalence of ANA at a titer of ≥1:80 and ≥ 1:160 was 8% and 4%, respectively, in HC; and it was 12% and 6% respectively, in MMP patients. The prevalence of anti-dsDNA was 0% in HC and 3% in MMP patients. When using HC sera for the diagnosis of SLE, the sensitivity of ANA at a titer of ≥ 1:80 and ≥ 1:160 was 98% and 90%, respectively, with specificity of 92% and 96%, respectively. The specificity decreased to 88% and 94%, respectively, when using sera from MMP patients. The specificity of anti-dsDNA was 100% and 97%, when using sera from HC and MMP patients, respectively.

ANA and anti-dsDNA gave high sensitivity and high specificity in patients with SLE







2) Please go through the two thesis presentations below and answer the questions below by also discussing them with the presenters:


https://youtu.be/sw8o8y5Yw_I



a)What was the research question in the above thesis presentation? 


Could hypomagnesemia in type 2 DM lead to further more complications


b) What was the researcher's hypothesis? 


According to the presenter, hypomagnesemia in type 2 diabetes mellitus could lead to further more complications and poor prognosis.



c)What is the current available evidence for magnesium deficiency leading to poorer outcomes in patients with diabetes? 


Association of serum magnesium with Type 2 Diabetes Mellitus



https://ijmrr.medresearch.in/index.php/ijmrr/article/view/302/590


This study was a prospective study done over a period of one month from March 1st to march 31st 2015.


P - 132 patients with Type 2 DM who were treated in the month march 2015 were included in the study.

They were divided into groups based on the duration of diabetes.


Group I (less than 5 years), group II (5 to 9 years) and group III (10 & more than 10 years)

72 patients (54.54%) were in group I and 30 of these were newly diagnosed.

22(15.90%) were in group II.

39(29.54%) were in group III and out of this 9 had DM for more than 20 years



The study states a significant decrease in the serum magnesium levels in patients with Type 2 DM, in poor glycemic status and with multiple micro-macro vascular complications, it is important to insist magnesium supplementation on uncontrolled Type 2 diabetes.



Oral Magnesium Supplementation Improves Insulin Sensitivity and Metabolic Control in Type 2 Diabetic Subjects


https://care.diabetesjournals.org/content/26/4/1147#:~:text=In%20conclusion%2C%20oral%20magnesium%20supplementation,thus%20contributing%20to%20metabolic%20control.


A randomized double-blind placebo-controlled trial

P- 63 subjects withType 2 Diabetes Mellitus and low serum magnesium

I- 32 (91.4%) subjects who received MgCl2 group

C- 31 (88.6%) subjects in the placebo group

O-

'In this study, subjects who received magnesium supplementation showed an important increase in serum magnesium concentration (15.5%) and reductions of fasting glucose (−37.5%), HbA1c (−30.4%), and HOMA-IR index (−9.5%) that were more significant than those observed in control subjects, despite the fact that time since diagnosis of diabetes, doses and type of hypoglycemic drugs used, and lifestyle intervention were similar. 


In this regard, although serum glucose (−27.5%) and HbA1c (−14.4%) levels were reduced in control subjects, HOMA-IR index (6.4%) increased and there were no significant variations in serum magnesium levels (−1.3%). This could be explained by taking into account the fact that control subjects remained with impaired metabolic control (average serum glucose and HbA1c 10.3 mmol/l and 10.1%, respectively), one of the most important sources for magnesium reduction. These findings support the necessity of oral magnesium supplementation to achieve an increase in serum magnesium concentration and to improve insulin sensitivity in type 2 diabetic subjects with decreased serum magnesium levels.'


Association of serum magnesium with type 2 diabetes mellitus and diabetic retinopathy


https://jfmpc.com/article.asp?issn=2249-4863;year=2019;volume=8;issue=5;spage=1671;epage=1677;aulast=Kumar


Out of 250 patients, Patients were divided based on serum magnesium level ≤ 1.7 mg/dL (group 1) and > 1.7 mg/dL (group 2).

110 patients (44%) were found to have hypomagnesemia. Glycemia by fasting blood sugar (P = 0.02), post-Prandial blood sugar (P = 0.04), and HbA1C(P = 0.01) was poorly controlled in hypomagnesemia group. 

In group 1, 62.7% had non proliferative diabetic retinopathy and 21.8% had proliferative diabetic retinopathy, whereas in group 2, 14.3% had nonproliferative diabetic retinopathy and 8.6% had proliferative diabetic retinopathy.


A) Clinically, hypomagnesemia may be defined as a serum Mg concentration ≤1.6 mg/dl.


Hypomagnesemia occurs at an incidence of 13.5 to 47.7% among patients with type 2 diabetes. Poor dietary intake, autonomic dysfunction, altered insulin metabolism, glomerular hyperfiltration, osmotic diuresis, recurrent metabolic acidosis, hypophosphatemia, and hypokalemia may be contributory. Hypomagnesemia has been linked to poor glycemic control, coronary artery diseases, hypertension, diabetic retinopathy, nephropathy, neuropathy, and foot ulcerations.


Hypomagnesemia been associated with type 2 diabetes, but also numerous studies have reported an inverse relationship between glycemic control and serum Mg levels.


 Although many authors have suggested that diabetes per se may induce hypomagnesemia, others have reported that higher Mg intake may confer a lower risk for type 2 diabetes . It is interesting that the induction of Mg deficiency has been shown to reduce insulin sensitivity in individuals without diabetes, whereas Mg supplementation during a 4-wk period has been shown to improve glucose handling in elderly individuals without diabetes . In patients with type 2 diabetes, oral Mg supplementation during a 16-wk period was suggested to improve insulin sensitivity and metabolic control .


The mechanisms whereby hypomagnesemia may induce or worsen existing diabetes are not well understood. Nonetheless, it has been suggested that hypomagnesemia may induce altered cellular glucose transport, reduced pancreatic insulin secretion, defective postreceptor insulin signaling, and/or altered insulin–insulin receptor interactions 


- Clinically, there are significant data linking hypomagnesemia to various diabetic micro- and macrovascular complications.




Cardiovascular : 


In a study that involved 19 normotensive individuals without diabetes, 17 hypertensive individuals without diabetes, and 6 hypertensive individuals with diabetes, Resnick et al. documented the lowest mean intracellular Mg concentration among the last group. Similarly, based on data from the Atherosclerosis Risk in Communities (ARIC) Study, a multicenter, prospective cohort study that lasted 4 to 7 yr and involved 13,922 middle-aged adults who were free of coronary heart disease at baseline, an inverse association between serum Mg and the risk for coronary heart disease was observed among men with diabetes .




Diabetic Retinopathy.


The link between hypomagnesemia and diabetic retinopathy was reported in two cross-sectional studies that involved both “insulin-dependent” patients and patients with type 2 diabetes. Not only did patients with diabetes have lower serum Mg levels compared with their counterparts without diabetes, but also the serum Mg levels among the cohort with diabetes had an inverse correlation with the degree of retinopathy . A similar link, however, was not observed when Mg was measured within mononuclear cells. In a study that involved 128 patients with type 2 diabetes and poor glycemic control (glycosylated hemoglobin >8.0%), intramononuclear Mg concentrations were not observed to be lower among those with diabetic retinopathy but rather among those with neuropathy and coronary disease .




Foot Ulcerations.


Given the link between hypomagnesemia and risk factors for the development of diabetic foot ulcers (e.g., polyneuropathy, platelet dysfunction), Rodriguez-Moran and Guerrero-Romero suggested that hypomagnesemia may be associated with an increased risk of diabetic foot ulcers. Indeed, they observed a higher incidence of hypomagnesemia among their patients with diabetic foot ulcers compared with those without the condition (93.9% of the 33 patients with diabetic foot ulcers compared with 73.1% of the 66 patients without diabetic foot ulcers; P = 0.02).




Nephropathy.


In a comparative study that involved 30 patients who had type 2 diabetes without microalbuminuria, 30 with microalbuminuria, and 30 with overt proteinuria, Corsonello et al. observed a significant decrease in serum ionized Mg in both the microalbuminuria and overt proteinuria groups compared with the nonmicroalbuminuric group. Accordingly, in a recent retrospective study, an association between low serum Mg levels and a significantly faster rate of renal function deterioration in patients with type 2 diabetes was reported .




Others.


Finally, there also are data to suggest the association between hypomagnesemia and other diabetic complications, including dyslipidemia and neurologic abnormalities .


https://cjasn.asnjournals.org/content/2/2/366



3) Please critically appraise the full text article linked below:


https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2796.2003.01233.x


What is the efficacy of aspirin in stroke in your assessment of the evidence provided in the article. Please go through the RCT CASP checklist here https://casp-uk.net/casp-tools-checklists/ and answer the questions mentioned in the checklist in relation to your article. 






The main results of the trial showed that aspirin treatment did not significantly reduce the rate of stroke progression. The progression rate was 15.9% amongst patients treated with aspirin and 16.7% for those on placebo.


The ability to live at home, to walk unaided, or need for further institutionalized care after discharge was not significantly improved in the aspirin group .


RCT CASP checklist:

https://documentcloud.adobe.com/link/review?uri=urn:aaid:scds:US:8d251179-8d1c-435c-803e-0daf96229a3f



4.Learning experience in this month

Posted in ICU

a.evaluated and managed a case of tubercular meningitis,performed lumbar puncture for that patient

b.Managed a case of CKd on MHd intubated in view of falling sats,cardiogenic pulmonary edema,learned about weaning off a patient from ventilator,ventilator settings from my seniors.The patient was to be reintubated in view of pco2 retension.I performed the reintubation.

c.i have put 2 femoral venous catheterisations,one IJV  central venous catheterisation

d.assisted in pericardiocentesis in a female pt with moderate pericardial effusion and cardiac tamponade, performed review echo on her and saw the echocardiographic features of pericardial effusion.





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