Prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) for the prevention and control of peritoneal metastasis in patients with gastrointestinal malignancies: a systematic review of randomized controlled trials.

Peritoneal metastasis is associated with poor prognosis, with studies in the literature reporting the survival of peritoneal metastasis without treatment to be three to six months. Hyperthermic intraperitoneal chemotherapy (HIPEC) has shown positive outcomes by improving the prognosis in patients with gastrointestinal malignancies. This systematic review of randomized controlled trials was done to determine the prophylactic role of hyperthermic intraperitoneal chemotherapy in preventing and controlling peritoneal metastasis gastrointestinal origin. Randomized controlled trials published between January 2019 to June 2021 were included. The databases used were MEDLINE (PubMed), EMBASE (Ovid), and the Cochrane library. Cochrane handbook for systematic review of intervention was used to assess the risk of bias in included trials. The results were reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. A total of five trials met the inclusion criteria. Two studies were on patients with gastric cancer, and the other three studies were on patients with colorectal cancer. HIPEC was given to a total of 116 gastric cancer patients and 308 colorectal cancer patients. In all the included studies on patients with gastric cancer, the peritoneal recurrence-free survival was significantly higher in the group that received HIPEC. There was no significant improvement in peritoneal-free survival in patients with colorectal cancer who received HIPEC. HIPEC appears to be effective in preventing peritoneal metastasis in patients with locally advanced gastric cancer without minimal postoperative complications. However, in patients with advanced colorectal malignancy, HIPEC does not seem to play a crucial role in preventing and controlling peritoneal metastasis.

Is Single-Dose Antimicrobial Prophylaxis Sufficient to Control Infections in Gastrointestinal Oncological Surgeries?

Surgical site infections (SSIs) represent one of the most important complications occurring postoperatively following surgical procedures. The SSI incidence is higher following gastrointestinal (GI) surgeries compared to any other surgery. It contributes to the majority of morbidity and mortality in patients undergoing GI surgeries. The accepted practice worldwide for the prevention and control of SSIs is providing antimicrobial prophylaxis. The appropriate antimicrobial and dose are chosen depending on the microbial flora, complications, and patient risk factors. The objective of this review was to determine the sufficient number of prophylactic antimicrobial doses that would be efficacious and safe in controlling the SSIs following GI oncological surgeries. Single-dose antimicrobial prophylaxis has shown the same efficacy as the multiple-dose antimicrobial regimen in controlling SSIs in esophageal, gastric, and colorectal surgeries. The advantages of a single-dose regimen include less chance of emergence of resistance, less chance for allergies or toxicity, and less cost. The addition of metronidazole with single-dose antimicrobial prophylaxis in colorectal surgery should be considered due to its beneficial effect in further reducing infections. Further randomized controlled trials are needed for the literature to determine the efficacy and safety of single-dose antimicrobial prophylaxis in patients undergoing esophageal and colorectal surgeries. In addition, studies are required to determine the individual effectiveness of metronidazole in controlling SSIs in colorectal surgeries.

Neuroimaging in Dementia: A Brief Review.

Dementia is a clinical syndrome that manifests itself with impairment in cognitive functions owing to various neurodegenerative etiologies causing severe disability in the older population. Although the diagnosis is largely dependent on clinical examination, biomarkers can significantly aid in early diagnosis of dementia, especially in those without any clinical evidence of neurocognitive impairment. These biomarkers can be discovered in cerebrospinal fluid (CSF) or can be assessed by neuroimaging. Our goal was to discuss and assess the role of different neuroimaging techniques in the early diagnosis of relatively common etiologies of dementia. We used PubMed as search engines to look for helpful articles; most of the sources used were peer reviewed. We discussed the utility of various neuroimaging techniques, such CT, MRI, positron emission tomography (PET) scan, and single-photon emission computed tomography (SPECT), in the diagnosis of dementia. We concluded that various modern neuroimaging techniques prove to be very helpful in early identification, diagnosis, and differentiation between subtypes. However, the actual clinical utility of these tests in terms of their cost-effectivity and availability remains to be seen. Ongoing research is required to further develop biomarkers for early identification and monitor the progression of different etiologies of dementia.

Parkinsonism: A Rare Adverse Effect of Valproic Acid.

Valproic acid (VPA) is an anti-epileptic drug (AED) used as a first-choice agent for most forms of epilepsy. It is used in the treatment of manic episodes, bipolar disorder, migraine prevention, and impulse control. Hence it is one of the most commonly prescribed drugs by physicians nowadays. VPA acts by increasing gama amino butyric acid (GABA) levels, and also reduces neuronal activation by blocking voltage-gated sodium, potassium, and calcium channels. VPA has various adverse effects like thrombocytopenia, hyperammonemia, teratogenicity causing spina bifida in newborns when exposed in utero. The focus of this review is to research one such easily overlooked adverse effect of VPA, which is VPA-induced Parkinsonism. We carried out a review of literature and gathered all comprehensive peer-reviewed articles from PubMed. The data for this research were collected ethically and legally after a thorough examination of the literature. Data obtained from the studies have suggested that Parkinsonism is an adverse effect of VPA. Chronic usage of VPA causes Parkinsonism. It occurs equally in males and females, more common in older people usually above the age of 55 years and not dose-dependent. According to the data obtained, all patients who developed Parkinsonism had serum levels in the therapeutic range (50-100 mcg/mL). Thus the chronic intake of maintenance dose of VPA seems to be the leading cause. The symptoms usually improve over a few weeks and fully resolve in a few months after stopping the drug. When the patient's symptoms do not improve, it means VPA has unmasked the underlying potential for developing Parkinson's disease. Such patients benefit from levodopa therapy. However, the mechanism of how VPA causes Parkinsonism remains unknown. Based on the articles reviewed, we hypothesize that VPA's mechanism of neuronal inactivation by blocking membrane channels across the neuronal membrane, primarily when used chronically could be the mechanism by which it causes Parkinsonism. VPA causes down regulation of sodium and potassium channels on neuronal membrane in order to stop the neurons from firing. Thereby a decrease in action potential across the neurons causes a temporary physiological inactivation of the neuron. When multiple neurons are inactivated in the basal ganglia of the brain, the patient develops symptoms of Parkinsonism. As the neurons are only temporarily inactivated physiologically, when the drug is stopped the membrane receptors are reactivated on the neuronal membranes. This leads to neuronal activation and neuronal membrane potential becomes the same as before. The above mechanism clarifies why the symptoms settle down when the medication is stopped.