临床研究杂志

Does genotypic vs. phenotypic segmentation make sense in the context of an amyotrophic lateral sclerosis (ALS) study?

It’s a provocative question, but one that warrants consideration. Research into the nature of ALS points to genetic mutations, often taking the form of miss aggregated or misfolded proteins. More than 20 genes have been causally linked to ALS. Four genetic mutations are common; the others are relatively rare . Certain genetic mutations appear to run in families but the same mutations can also be found in sporadic (i.e., non-familial) cases. These mutations have formed the basis for past patient segmentation efforts but there is reason to question whether such segmentation efforts have any relevance to the presentation of ALS itself. Do these genetic mutations actually express different phenotypes? Do they play any role in the sign, symptoms, or trajectories of the disease? Conversely, do therapies targeting the identified genes- even if they could effectively correct the physiological consequences of a specific mutation-actually have an effect on ALS in the patient?

The recent history of drug development offers mixed answers to these questions. In the world of oncology, targeted, personalized genetic therapies are producing compelling outcomes . Conversely, targeted therapeutic development for ALS has largely been ultimately unsuccessful, despite promising early phase clinical results . It may be that targeted therapies in oncology have been successful because the underlying biology of different cancers is more fully understood. In contrast, much remains unknown about the underlying biology of ALS . Further, treatment of a systemic disease such as ALS may inherently be more difficult than treatment of a disease with a specific target such as a solid tumor with a discreet set of genetic mutations as may be the case in oncology.

While many genetic mutations in ALS have been identified and studied, and while the phenotypic presentations of ALS are identifiable and agreed upon, the connections between genotype and phenotype remain incomplete. As efforts to find therapies targeting ALS continue down both paths, it becomes increasingly important for members of the clinical and research communities to develop a better understanding of where and how genotype and phenotype are linked, particularly because the links between phenotype and genotype can affect the design and conduct of ALS clinical trials in critical ways.

Genetic carrier screening finds a new place in clinical practice today. Consequent to advanced technology coupled with increased awareness among population in the reproductive age group, this seems to be gaining popularity. Indian population is a heterogeneous mix of several sub-populations and the gene pool is quite different from the western or oriental populations. Thus, a need to detect carrier frequency was felt and a pilot study was performed at a tertiary care hospital in North India, on 200 healthy individuals. The study brought out some unexpected results, such as the high frequency of cystic fibrosis in Indian population. This mini-review provides a glimpse into the study and puts together the carrier frequencies of common autosomal recessive disorders as detected from other studies as well.

Purpose: Blood transfusion in breast cancer surgery patients is now quite rare as surgical haemostatic techniques have become very meticulous. In our hospital, all patients planned for mastectomy have a routine blood cross match done preoperatively. The cost of this blood cross match comes down as about 10 United States dollars (USD) per patient. In this study, we looked at our mastectomy patients who required blood transfusion.

Methods: All mastectomy patients from January 2016 to June 2016 were included in our study. The data was derived from a prospectively maintained computerized database. Patient demographics, preoperative and postoperative haemoglobin levels, reasons and timings of blood transfusion were recorded.

Results: 182 patients had mastectomy during 6 months. 170 (93.4%) patients had preoperative blood crossmatch done. 15 patients (8.2%) required blood transfusion preoperatively. This was primarily for building up their haemoglobin levels (range 7.4-9.9 g/dL, mean 9.1 g/dL). 9 out of 15 of these patients underwent neoadjuvant chemotherapy.

Cost of blood crossmatch in these 15 patients needing transfusion was 150 USD compared to 1700 USD cost of cross matching all 170 patients. None of our patients required transfusion intra or post-operatively. Cost of blood crossmatch in 155 patients that never required blood transfusion was 1550 USD.

Conclusion: None of our mastectomy patients required blood transfusion in an emergency situation. 8.2% patients needed transfusion preoperatively, where there was ample time to crossmatch and arrange blood. We recommend that routine preoperative crossmatch in mastectomy patients can be safely avoided (with an additional benefit of saving cost 1550 USD over 6 months).

Background: Thalassemia is an inherited genetic hemoglobin disorder wherein, afflicted child is born when both parents are carriers for defective alpha or beta hemoglobin gene. The thalassemias are the most common genetic disorder on a worldwide basis. The requirement of frequent blood transfusions in these patients pose a substantial burden on the health care system.

Methods: A prospective observational study was conducted across 6 months (July 2018-December 2018) in a tertiary care hospital, Pune. The present study included 30 registered patient and their past 6 months record of blood transfusion (esp frequency), previous hemoglobin levels, height and weight. All these parameters were compared 6 months after supplementation with omega 3 fatty acids and proteins.

Results: 16 of 28 patient showed that the average durations between two blood transfusions was increased by minimum 01 day to a maximum of 5 days. The average number of blood bag required was less than required blood bags in the period of pre supplementation. 20 of 28 patients showed a rise in hemoglobin level from a range of 0.5 to 1.2 gm/dl.

Conclusion: In a country like India, with the high frequency of hemoglobinopathies, causing increased burden on the society, it is necessary to control the incidence by effective steps. Low cost and easily administered supplementation by omega 3 fatty acid and proteins may reduce the requirement of repeated blood transfusion along with increase in hemoglobin level.