Women with Epilepsy: Anti-epileptic Drugs and Perinatal Outcomes.

Epilepsy is a chronic neurological condition that requires treatment throughout the pregnancy. Seizures should be well controlled before conception with a specific type of anti-epileptic drug (AED) for each epileptic syndrome. The selection of AED is crucial in women with epilepsy (WWE). AEDs with the lowest malformations rates should be used for treatment during pregnancy. Valproate should be avoided in WWE of childbearing age as it is associated with the highest risk of neurocognitive malformations. However, pregnancy might alter the levels of AEDs, which can lead to an increase in seizure frequency. It is important to monitor AED levels and make necessary dose adjustments to control seizures during pregnancy. WWE should be treated with the lowest possible dose allowed and preferably with a single AED to avoid harmful effects on the developing fetus. Women should be counseled to take folic acid during pregnancy as it reduces the risks for cardiovascular, genitourinary, and neural tube defects. Generally, WWE usually have normal pregnancies and can bear healthy offspring. Pregnant women need continuous follow-up in a coordinated manner with the neurologist and obstetrician to assess for adverse pregnancy and fetal outcomes.

Cancer of Unknown Primary: A Review on Clinical Guidelines in the Development and Targeted Management of Patients with the Unknown Primary Site.

Cancer of unknown primary (CUP) is a malignant widespread metastatic disease without an identifiable primary site after extensive clinical investigation. Recently, a decline is observed in the diagnosis of CUP, mainly due to improvement in detection of the primary tumors, thus decreasing the unknown primaries. Worldwide, CUP is the sixth to eighth most common malignancy, accounting for 2.3% to 5% of a new cancer diagnosis. CUP is third to fourth most common cause of death due to cancer-related mortality. The prognosis of CUP is depressing with the median survival of three to six months in the previous studies, but according to recent studies, median survival is less than one year. High risk for developing CUP is seen in heavy smokers (26 or more cigarettes/day) and individuals with the lowest quartiles of waist circumference. A weak association is observed with the use of alcohol consumption and low level of education. Human papillomavirus DNA plays a role in those with squamous cell carcinoma of unknown primaries in head and neck regions. In the diagnosis of CUP, comprehensive medical history, complete physical examination (including genitourinary, rectal exam, and breast examination in women) and necessary laboratory tests are crucial. Whole-body positron emission tomography-computed tomography (PET/CT) is the investigation of choice to assess the entire body for CUP. Multiparametric 3T-MRI (MP-MRI) is used to examine the local soft tissue status, helps in the staging of the tumor, and to determine the extent of involvement of tissue for medical as well as prognostic purposes. Immunohistochemistry outlines the specific markers, including caudal-related homeobox protein (CDX2), homeobox protein Nkx-3.1 (NKX3-1), paired box gene 8 (PAX8), special AT-rich sequence-binding protein 2 (SATB2), thyroid transcription factor 1 (TTF-1), and splicing factor 1 (SF1) with the focus on the effectiveness of lineage-restricted transcription factors. Patients response to treatment can be evaluated by the gene expression profiling (GEP) test that also predicts tissue of origin (TOO). Tumor identified through gene profiling is sensitive to platinum/taxane therapy, others that are not TOO tumors are resistant to platinum/taxane. The new therapeutic method based on molecular profiling is associated with higher treatment response. In comprehensive genomic profiling, it is observed that there is at least one clinically appropriate genomic alteration in CUP that can influence the targeted therapy. The targeted therapeutic approach will not only improve the disease outcome but will also be cost-effective and save time from finding the primary site.

Single-best Choice Between Intermittent Versus Continuous Renal Replacement Therapy: A Review.

Critically ill patients often develop multiorgan dysfunction syndrome. Acute kidney injury (AKI) is part of it. Renal replacement therapy (RRT) remains the primary choice of treatment in severely ill patients who develop AKI. Recent data have shown increased use of RRT in AKI patients. Therefore, the right choice of RRT plays an important role in the renal recovery of such patients. The question of which mode of RRT to apply has been the topic of study in the last two decades. Whether RRT should be conducted in intermittent mode, as intermittent hemodialysis (IHD), or in continuous mode, as continuous renal replacement therapy (CRRT), is still being investigated. CRRT has a hypothetical advantage when compared to IHD, as it involves a process in which there is gradual removal of fluids, better control of urea, better maintenance of the acid/base balance, and hemodynamic stability. However, IHD is more practical, cost-effective, does not require anticoagulation, decreases the bleeding risk, and removes the solute efficiently and rapidly in acute life-threatening conditions. Other modalities of RRT like sustained low-efficiency daily dialysis (SLEDD) and prolonged intermittent renal replacement therapy (PIRRT) have shown to encompass the benefits of both CRRT in terms of hemodynamic stability and IHD in terms of cost-efficiency. Although SLEDD is progressively being used as an alternative to CRRT and IHD, very few studies have shown to support it. In this article, we try to summarize the advantages and disadvantages of the different techniques used in RRT. With SLEDD gaining more popularity among the different modalities of RRT, we want to assess the possibility of its routine implementation as the single-best choice for RRT.

Efficacy and Safety of Stem Cell Therapy in Advanced Heart Failure Patients: A Systematic Review with a Meta-analysis of Recent Trials Between 2017 and 2019.

Objective The effects of stem cell therapy in patients with advanced heart failure is an ongoing debate. This study aimed to assess the effectiveness and safety of stem cell therapy plus the standard of care as compared to the placebo plus the standard of care in advanced heart failure patients. Methods A comprehensive keyword search of PubMed between 2017 and 2019 was performed to extract trials conducted with stem cell therapy controlled with placebo in advanced heart failure. We included randomized controlled trials (RCTs) with data on safety and efficacy in patients with advanced heart failure after stem cell transplantation. Results Six RCTs, consisting of 569 patients, were selected. Three-hundred sixty-seven (367) out of 369 participants from the eligible four out of six RCTs were included for efficacy analysis, as we lost two patients from the final analysis due to early death. Five-hundred twenty-six (526) out of 527 participants from the eligible five out of six RCTs were included for safety analysis, as we lost one patient from the final analysis for not being able to receive the intervention. Stem cell transplantation significantly improved left ventricular ejection fraction (LVEF) by 4.58% (95% CI: 3.73-5.43%; p = 0.00001), improved left ventricular end-systolic volume (LVESV) by -5.18 ml (95% CI: -9.74 to -0.63 ml; p =0.03), and there was no difference in the risk of all-cause mortality (OR 0.97; 95% CI: 0.52 to 1.78%; p = 0.91). The above results correlate with the previous meta-analysis data conducted in 2016. Conclusions This meta-analysis provided the cumulative efficacy and safety results of stem cell transplantation in advanced heart failure based on recent RCTs. The above results suggest that stem cell therapy was associated with a moderate improvement in LVEF, and the safety analysis indicates no increased risk of mortality in patients with advanced heart failure. This meta-analysis recommends conducting more RCTs comparing stem cell transplantation and placebo with a larger patient population and longer follow-up.

Drug-induced Reduction of Gamma Carboxylation in Osteocalcin: What is the Fallback?

Osteoporosis is a medical condition in which bone becomes fragile and weak. In this condition, the quality and density of the bone are reduced. Vitamin K is vital for bone mineralization as it plays a vital role in the gamma-carboxylation of osteocalcin. Therefore, if there is a deficiency of vitamin K, it can lead to osteoporosis due to undercarboxylated osteocalcin. Warfarin is the most widely used anticoagulant in the elderly. In this article, we reviewed how Warfarin, an inhibitor of vitamin K, affects bone remodeling and leads to osteoporosis.

Anaphylactic Reaction to Cyanocobalamin: A Case Report.

Vitamin B12 is essential for the development of healthy nerves and red blood cells. Vitamin B12 deficiency is becoming widespread and most commonly affects elderly, pregnant women, vegetarians, and patients with renal or intestinal diseases. Either parenteral vitamin B12 treatment or high-dose oral vitamin B12 treatment is an effective therapy regardless of etiology. Parenteral therapy using the intramuscular route is considered the most familiar treatment for vitamin B12 deficiency. Anaphylactic reaction after intramuscular injection is an uncommon and potentially serious side effect. In this study, we are documenting a case of anaphylactic reaction in a 55-year-old woman after her second dose of intramuscular injection of cyanocobalamin. The purpose of this case report is to highlight the need to understand the rare life-threatening side effect of intramuscular cyanocobalamin. Health care providers should be vigilant while administering the intramuscular injection of cyanocobalamin to vitamin B12 deficient patients.

Post Vaccination Guillain Barre Syndrome: A Case Report.

Guillain-Barre syndrome is a rare but fatal autoimmune disease. The exact cause of Guillain-Barre syndrome is still unknown. The most common known etiology of Guillain-Barre syndrome is infectious disease notably caused by Campylobacter jejuni. A very small fraction of people can develop Guillain-Barre syndrome due to vaccines and vaccinations like a meningococcal vaccine, poliovirus vaccine, influenza vaccine, and rabies vaccine. Of all these, rabies is fatal invariably. It can be preventable if diagnosed early and post-exposure treatment is followed according to the World Health Organization guidelines. Older formulations of rabies vaccines are cultured in the neural tissues and have been found to have an increased risk of Guillain-Barre syndrome. Although less immunogenic older formulations of rabies vaccines are more commonly used in Asian and South American countries due to their cost-effective nature. There is little to no data available on the incidence of Guillain-Barre syndrome due to vaccinations in Pakistan. Most of the cases of Guillain-Barre syndrome due to vaccination are either undiagnosed or misdiagnosed. In this case report, we are presenting a case of vaccine-associated Guillain-Barre syndrome due to neural tissue anti-rabies vaccine in a young girl, who presented with lower limb weakness, inability to pass urine and abdominal pain.