MDMA-Based Psychotherapy in Treatment-Resistant Post-Traumatic Stress Disorder (PTSD): A Brief Narrative Overview of Current Evidence.

Post-traumatic stress disorder (PTSD) is a debilitating mental health disorder that causes significant dysfunction in individuals. Currently, there are many approved pharmacotherapy and psychotherapy treatment options for PTSD, but unfortunately, half of the patients do not respond to traditional therapies. In this article, we review clinical trials and research on 3,4-methylenedioxymethamphetamine (MDMA)-assisted psychotherapy in PTSD patients, its pharmacokinetics, and current treatment guidelines for PTSD. Our findings are based on the results of the efficacy of MDMA-assisted psychotherapy from six phase II randomized controlled trials. MDMA-assisted psychotherapy for PTSD has received the "breakthrough therapy" designation from the FDA. MDMA can reduce PTSD symptoms even in treatment-resistant cases by increasing certain neurohormones, i.e., dopamine, serotonin, norepinephrine, and oxytocin. It also modulates activities in the brain regions involved in fear and anxiety. Future research is needed to show whether the advantages outweigh the disadvantages and whether its use can be integrated into available treatment options for PTSD.

Efficacy and safety of antibody-drug conjugates in triple-negative and HER-2 positive breast cancer: A systematic review and meta-analysis of clinical trials.

Breast cancer (BC) is the 2nd most common cause of cancer-related deaths. Antibody-drug conjugates (ADCs) are monoclonal antibodies linked to cytotoxic agents and are directed towards a specific tumor protein. Therefore, they are more potent and can have relatively less toxicity. In this meta-analysis, we assessed the efficacy and safety of ADCs in breast cancer. We searched PubMed, Cochrane, Web of Science, and clinicaltrials.gov for relevant studies and included 7 randomized clinical trials (N = 5,302) and 7 non-randomized clinical trials (N = 658). R programming language software was used to conduct this meta-analysis. In 4 RCTs on HER-2 positive BC (N = 2,825), the pooled HR of PFS and OS was 0.72 (95% CI = 0.61-0.84, I2 = 71%) and 0.73 (95% CI = 0.64-0.84, I2 = 20%), respectively in favor of ADCs versus chemotherapy. In RCT on triple negative BC (N = 468), HR of PFS and OS were 0.55 (95%CI = 0.51-0.61) and 0.59 (95% CI = 0.54-0.66), respectively, in favor of saci-gov versus chemotherapy. In RCT on HER-2 positive residual invasive BC, HR of recurrence/death was 0.61 (95% CI = 0.54-0.69) in favor of ADC versus chemotherapy. In an RCT (N = 524), the HR of PFS and OS were 0.28 (95% CI = 0.22-0.37) and 0.55 (95%CI = 0.36-0.86), respectively, in favor of trastuzumab-deruxtecan (T-der) as compared to trastuzumab-emtansine (T-DM1). Anemia, rash, diarrhea, fatigue, hypertension, thrombocytopenia, and elevated aminotransferases were the common ≥grade 3 adverse events reported in 4%, 1%, 2%, 1%, 2%, 9%, and 3% of the patients, respectively. ADCs were more effective than single and double agent chemotherapy in patients with HER-2 positive or triple negative BC. Among ADCs, T-der was more effective than T-DM1.

Efficacy and Safety of Checkpoint Inhibitors in Clear Cell Renal Cell Carcinoma: A Systematic Review of Clinical Trials.

Renal cell carcinoma (RCC) is the most common kidney cancer in adults (approximately 90%), and clear cell RCC (ccRCC) is the most frequent histologic subtype (approximately 75%). We reviewed the safety and efficacy of checkpoint inhibitors (CPIs) in ccRCC, identifying 5927 articles in PubMed, Embase, Cochrane, and Web of Science. Ten randomized control (N = 7765) and 10 non-randomized (N = 572) studies were included. Overall, 4819 patients treated with CPI combinations were compared with everolimus, sunitinib, or placebo. Overall response rates (ORR) were 9-25% with nivolumab (niv), 42% with niv + ipilimumab (ipi), 55.7% with niv + cabozantinib, 56% with niv + tivozanib vs. 5% with everolimus. ORR was 51.5-58% with avelumab + axitinib vs. 25.5% with sunitinib. ORR was 59.3-73% with pembrolizumab + tyrosine kinase inhibitor vs. 25.7% with sunitinib. ORR was 32-36% with atezolizumab + bevacizumab vs. 29-33% with sunitinib. In patients with PD-L1+ve and -ve ccRCC, niv, atezolizumab, ipi, and pembrolizumab were safe and effective alone and when combined with cabozantinib, tivozanib, axitinib, levantinib, and pegilodecakin. Atezolizumab + bevacizumab was safe and effective in ccRCC with high PD-L1 expression. Pembrolizumab was safe and effective in preventing recurrence in ccRCC patients with nephrectomy. Additional randomized, double-blind, multicenter clinical trials are needed to confirm these results.

Continuous Glucose Monitoring Versus Self-monitoring of Blood Glucose in Type 2 Diabetes Mellitus: A Systematic Review with Meta-analysis.

Every eleventh adult has diabetes, and every third has prediabetes. Over 95% of diabetics are of type 2. It is well established that diabetes doubles the risk of heart disease and stroke apart from increasing the risk of microvascular complications. Hence, strict glycemic control is necessary. However, it increases the risk of hypoglycemia, especially in patients with longstanding diabetes. Continuous glucose monitors (CGM) use a sensor to continuously measure the glucose levels in the interstitial fluid every 10 seconds and gives out mean values every five minutes. CGMs are emerging tools in the management of type 2 diabetes. The prime objective of this review is to find out if there is enough supporting evidence, suggesting that continuous glucose monitoring is more effective than self-monitoring of blood glucose (SMBG) in type 2 diabetes. We conducted a systematic literature search in Medline (PubMed) looking for any studies addressing our objective. It is observed that there is a varying level of evidence supporting that employing a CGM can reduce glycated hemoglobin (HbA1c), hypoglycemic events, and increase patient satisfaction. However, some studies reported no significant benefits. This systematic review with meta-analysis concludes that the use of CGM in type 2 diabetes mellitus (T2DM) is beneficial, as it significantly reduces HbA1c compared to the usual method of SMBG. The pooled mean difference in HbA1c was -0.25 (-0.45, -0.06) and statistically significant (at p = 0.01) when comparing CGM to SMBG.

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.

The Role of Warfarin and Rivaroxaban in the Treatment of Cerebral Venous Thrombosis.

Cerebral venous thrombosis (CVT) is a rare complication of hypercoagulable states such as pregnancy, lupus anticoagulant syndrome, systemic lupus erythematosus, Crohn's disease, ulcerative colitis, malignancies, and the use of oral contraceptive pills. It most commonly occurs in young people, especially women, but can occur in the elderly as well. The signs and symptoms vary from focal neurological deficiencies to alteration in mental status. In this review, we compare the efficacy and safety profile of traditional anticoagulants heparin and vitamin K antagonists (warfarin) to novel oral anticoagulants, which include rivaroxaban, apixaban, dabigatran. The advantages of the new anticoagulants are their effectiveness, short half-life, oral intake instead of parenteral, and the decreased need for constantly monitoring prothrombin time (PT), activated partial thromboplastin time (APTT), and the international normalized ratio (INR). In this review, we discuss studies that demonstrate that these novel oral anticoagulants are effective and safe in treating cerebral venous thrombosis without many adverse effects when compared with traditional treatment options. There are also some case reports that point towards the effectiveness of newer agents; however, we need more studies with bigger samples to reach a conclusion in favor of new oral anticoagulants. The studies that have already been conducted can become the basis for conducting newer studies that can revolutionize the modern treatment for conditions like CVT.

Dual or Mono Antiplatelet Therapy for the Prevention of Ischemic Stroke: A Literature Review.

Ischemic stroke is defined as a sudden loss of blood to the brain which results in deprivation of oxygen and other nutrients. It can be either a transient episode called as "transient ischemic attack" (TIA), or it could last longer than 24 hours giving rise to "infarction of tissues" in the central nervous system. Anti-platelet agents are widely used for the secondary prophylaxis of ischemic stroke, and amongst them, aspirin remains the drug of choice. In this literature review, we summarized the existing data regarding the ischemic type of strokes with particular attention to the use of antiplatelet agents for this purpose. The following review highlights the significance of the use of dual antiplatelet (aspirin and clopidogrel) regimen for the stroke prevention. The role of dual antiplatelet (aspirin and clopidogrel) in patients with a recent TIA (within 30 days) or severe stenosis (70%-99%) of a major intracranial artery, for 90 days, might be a beneficial approach.