Sufficient Treatment For Patients Research Articles

Molecular Mechanism of SLC6A8 Dysfunction with c.1699T > C (p.S567P) Mutation in Cerebral Creatine Deficiency Syndromes.

Cerebral creatine deficiency syndromes (CCDS) are neurodevelopmental disorders caused by a decrease in creatine levels in the central nervous system (CNS) due to functional mutations in creatine synthetic enzymes or creatine transporter (CRT/SLC6A8). Although SLC6A8 mutations have been reported to be the most frequent cause of CCDS, sufficient treatment for patients with CCDS harboring SLC6A8 mutations has not yet been achieved. This study aimed to elucidate the molecular mechanism of SLC6A8 dysfunction caused by the c. 1699T > C missense mutation, which is thought to induce dysfunction through an unidentified mechanism. A study on SLC6A8-expressing oocytes showed that the c.1699T > C mutation decreased creatine uptake compared to that in wild-type (WT) oocytes. In addition, a kinetics study of creatine uptake revealed that the c.1699T > C mutation reduced the maximum uptake rate but not Michaelis-Menten constant. In contrast, the c.1699T > C mutation did not attenuate SLC6A8 protein levels or alter its cellular localization. Based on the SLC6A8 structure in the AlphaFold protein structure database, it is possible that the c.1699T > C mutation alters the interaction between the S567 and Y143 residues of SLC6A8, leading to decreased creatine transport function. These findings contribute to the understanding of the pathology of CCDS and to the development of strategies for CCDS treatment.

β1-Adrenoreceptor Autoantibodies in Heart Failure: Physiology and Therapeutic Implications.

Antibodies that activate the β1-AR (β1-adrenoreceptor) can induce heart failure in animal models. These antibodies are often found in patients with heart failure secondary to varying etiologies. Their binding to the β1 receptor leads to prolonged receptor activation with subsequent induction of cellular dysfunction, apoptosis, and arrhythmias. β-blocker therapy while highly effective for heart failure, may not be sufficient treatment for patients who have β1 receptor autoantibodies. Removal of these autoantibodies by immunoadsorption has been shown to improve heart failure in small studies. However, immunoadsorption is costly, time consuming, and carries potential risks. An alternative to immunoadsorption is neutralization of autoantibodies through the intravenous application of small soluble molecules, such as peptides or aptamers, which specifically target and neutralize β1-AR autoantibodies. Peptides may induce immunogenicity. Animal as well as early phase human studies with aptamers have not shown safety concerns to date and have demonstrated effectiveness in reducing autoantibody levels. Novel aptamers have the potential advantage of having a wide spectrum of action, neutralizing a variety of known circulating G-protein coupled receptor autoantibodies. These aptamers, therefore, have the potential to be novel therapeutic option for patients with heart failure who have positive for β1-AR autoantibodies. However, clinical outcomes trials are needed to assess the clinical utility of this novel approach to treat heart failure.

Response to Rituximab Induction Is a Predictive Biomarker in Post-Transplant Lymphoproliferative Disorder (PTLD) and Allows Successful Treatment Stratification in an International Phase II Trial Including 152 Patients

Response to Rituximab Induction Is a Predictive Biomarker in Post-Transplant Lymphoproliferative Disorder (PTLD) and Allows Successful Treatment Stratification in an International Phase II Trial Including 152 Patients

Radiation therapy for older adults with glioblastoma: radical treatment, palliative treatment, or no treatment at all?

The incidence of glioblastoma in older adults has increased over the last few decades. Current treatment includes surgery, radiotherapy, and chemotherapy, but optimal disease management remains a matter of debate. Both standard (60 Gy in 30 daily fractions) and hypofractionated radiotherapy (30-40 Gy in 10-15 daily fractions) have been employed with a similar survival benefit. Recent randomized studies indicate that chemotherapy with the alkylating agent temozolomide is a safe and effective therapeutic option for patients aged 60 years or older with newly diagnosed glioblastoma, suggesting that it should be a sufficient treatment for patients presenting with a methylated O6-methylguanine-DNA methyltransferase (MGMT) promoter gene. The addition of concomitant temozolomide chemotherapy, adjuvant temozolomide chemotherapy, or both to postoperative radiotherapy, which is the standard treatment for adults with glioblastoma, has been associated with a survival benefit for older patients with a good performance status; however, aggressive treatment in this population may be associated with a high risk of neurological toxicity and deterioration of quality of life. Survival stratification according to age, MGMT promoter methylation status, and neurological status may be useful for clinical decision making and designing randomized trials for adequately evaluating the optimal combination of radiotherapy and chemotherapy for older patients with glioblastoma.

Oncological outcomes of transanal local excision for high risk T1rectal cancers

To evaluate the oncological outcomes of transanal local excision and the need for immediate conventional reoperation in the treatment of patients with high risk T(1) rectal cancers. Twenty five high risk T(1) rectal cancers treated by transanal local excision at the Guangdong General Hospital were analyzed retrospectively. Twelve patients received transanal local excision and 13 patients underwent subsequent immediate surgical rescue after transanal local excision within 4 wk. Differences in the local recurrence rates and 5-year overall survival rates between the two groups were analyzed. The prognostic value of immediate conventional reoperation for high risk T(1) rectal cancers was also evaluated. The median follow-up period was 62 mo. The local recurrence rates after transanal local excision for high risk T(1) rectal cancer were 50%. By immediate conventional reoperation, the local recurrence rates were significantly reduced to 7.7%. The difference between these two groups was statistically significant (P = 0.030). Kaplan-Meier survival analysis showed a trend for decreased 5-year overall survival rates for patients treated by transanal local excision compared with immediate conventional reoperation (63% vs 89%). Transanal local excision cannot be considered sufficient treatment for patients with high risk T(1) rectal cancers. Immediate conventional reoperation should be performed if the pathology of the local excision is high risk.

Leg ulcers: uncommon presentations

Uncommon presentations like vasculitis or other immunologic causes and malignancy account for about 1% to 2% of patients suffering from leg ulcers. We focus on such uncommon leg ulcers including: cutaneous vasculitis causing cutaneous ulceration, other immunologic or metabolic cutaneous lesions such as pyoderma gangrenosum and necrobiosis lipoidica, and ulcers based on neoplastic etiology. A short description on leg ulcers in the tropics is also included. The described uncommon presentations of leg ulcers are typically difficult to diagnose and treat; it is a specialist's job to take care of patients with these types of ulcers. Multidisciplinary specialized wound healing concepts integrated in the national health care system, as an accepted expert function, is the ideal way to organize the wound healing area. Such a system would result in an earlier diagnosis and more sufficient treatment for patients with uncommon presentations of leg ulcers.

Total abdominal hysterectomy and bilateral salpingo-oophorectomy. A sufficienttreatment for patients with low risk endometrial carcinoma

Leijon T; Rosenberg P; Boeryd B. Total abdominal hysterectomy and bilateralsalpingo-oophorectomy. A sufficient treatment for patients with low riskendometrial carcinoma. Int. J. Gynecol Cancer 1997; 7:376–380. In this prospective study, 248 surgical state I endometrial carcinomapatients with favorable prognostic factors were included. All patients weretreated only with total abdominalhysterectomy and bilateral salpingo-oophorectomy. The clinical outcome andrelapse rate were the endpoints. Only 3% of the patients recurred andthe total survival rate was96% during a median observation time of 42 months. We conclude that atotal abdominal hysterectomy and bilateral salpingo-oophorectomy is adequatetreatment for this groupof patients. In this material seven out of nine recurrences were detected byscheduled controls. Among the five patients with local recurrences, four wereasymptomatic and diagnosed during scheduled follow-up examination.

Two decades of experience with testicular tumors in children at St Jude Children's Research Hospital

From 1968 to 1988, 24 children and adolescents with malignant testicular tumors were treated at St Jude Children's Research Hospital. Pure yolk sac tumors (YST) were present in 13 cases; 11 patients had other types of nonseminomatous malignant germ cell tumors. Children with localized and totally resectable disease (stage I) were treated by orchiectomy alone; all others also received chemotherapy. Five of ten patients treated before the implementation of a multiagent chemotherapy protocol in 1979 have died. By contrast, all of the 14 patients treated on this protocol are alive. The improved survival during the past decade is attributable to better diagnostic imaging techniques, the availability of serum tumor markers to monitor disease activity, and more effective chemotherapy. Orchiectomy alone is sufficient treatment for patients with clinical stage I disease who show appropriate reductions in tumor marker levels after surgery. Modern platinum-based chemotherapy provides disease control in patients with higher stage disease.

DOUBLE-BLIND COMPARISON OF CAPTOPRIL ALONE AGAINST FRUSEMIDE PLUS AMILORIDE IN MILD HEART FAILURE

Captopril alone as therapy for mild heart failure was compared with a combination of frusemide and amiloride in a double-blind randomised crossover trial in 14 patients who had previously been treated with diuretics. Although 10 patients remained stable on captopril alone, 4 patients deteriorated, with the development of pulmonary oedema or breathlessness. All 4 patients had had pulmonary oedema previously, unlike the patients who remained stable. Angiotensin converting enzyme inhibition alone is not sufficient treatment for patients with mild heart failure and a history of overt pulmonary oedema.

Late results of perforated duodenal ulcer treated by simple suture

AbstractA study was performed of 156 patients who underwent follow‐up evaluations 3 to 23 years (mean 13 years) after simple closure of a perforated duodenal ulcer. Subsequent definitive ulcer surgery was indicated in 111 patients (71%) for severe recurrent dyspepsia. Bleeding, reperforation or pyloric obstruction occurred in 14 patients (9%). Among 33 patients (21%) with an ulcer history of less than 3 months prior to perforation, only 4 (12%) required further surgery while a subsequent operation was indicated in 107 of 123 patients with a longer ulcer history. Immediate definitive surgery is indicated for perforated duodenal ulcer in patients with ulcer symptoms for more than 3 months before perforation. Simple suture of the perforation is sufficient treatment for patients with a shorter ulcer history.