Contemporary National Patterns of Eligibility and Use of Novel Cardioprotective Antihyperglycemic Agents in Type 2 Diabetes Mellitus.

Background SGLT-2 (sodium glucose transporter-2) inhibitors and GLP-1RAs (glucagon-like peptide-1 receptor agonists) effectively lowered cardiovascular risk in large clinical trials for patients with type 2 diabetes mellitus at high risk for these complications, and have been recommended by guidelines. To evaluate the contemporary landscape in which these recommendations would be implemented, we examined the use of these medications according to clinical guideline practice. Methods and Results In the National Health and Nutrition Examination Survey for 2017 to 2018, we defined compelling indications for SGLT-2 inhibitors by the presence of atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease, and for GLP-1RAs by the presence of established or high-risk atherosclerotic cardiovascular disease, based on large clinical trials that have been incorporated in guideline recommendations of the American College of Cardiology and American Diabetes Association. We then evaluated use of these medications among patients with physician-diagnosed type 2 diabetes mellitus. All analyses incorporated complex survey design to produce nationally representative estimates. A total 1104 of 9254 sampled individuals had type 2 diabetes mellitus, representing 10.6% (95% CI, 9.7%-11.6%) of the US population or 33.2 million adults nationally. Of these, 52.6% (95% CI, 47.7%-57.5%) had an indication for SGLT-2 inhibitors, 32.8% (95% CI, 28.8%-37.2%) for GLP-1RAs, and 26.6% (95% CI, 22.2%-31.7%) for both medications. During 2017 to 2018, 4.5% (95% CI, 2.4%-8.2%) were treated with SGLT-2 inhibitors and 1.5% (95% CI, 0.7%-3.2%) with GLP-1RAs. Atherosclerotic cardiovascular disease, heart failure, or chronic kidney disease were not independently associated with SGLT-2 inhibitor or GLP-1RA use in patients with diabetes mellitus. Conclusions Despite a large number of patients being eligible for guideline-recommended cardiorenal protective therapies, there are substantial gaps in the use of SGLT-2 inhibitors and GLP-1RAs, limiting their public health benefits.

Venous Thromboembolism Has a Variable Time of Occurrence in the Course of COVID-19: A Case Series.

The novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) which results in coronavirus disease 2019 (COVID-19) has had a devastating impact globally. Not much is fully understood about this disease. Acute respiratory distress syndrome (ARDS) appears to be the commonest complication among patients with COVID-19. However, venous thromboembolism (VTE) appears to be a common complication among patients with COVID-19 even with adequate anticoagulation during hospitalization. VTE may confer a poor outcome on its own or may exacerbate other common complications such as ARDS or cardiac injury. There are several diagnostic dilemmas with regards confirming VTE among patients with COVID-19 as there is a move to reduce the transfer of patients for angiographic studies or even venous Doppler ultrasonography because of the high transmissibility SARS-CoV-2. There is also the risk of worsening ARDS following fluid administration to prevent contrast nephropathy after angiographic studies.  It is, therefore, crucial to understand the timing of VTE occurrence in the setting of COVID-19, identify strategies for early diagnosis of VTE, therapeutic options as well as prognostic implications of VTE in the setting of COVID-19.

Necessity of therapy for post-thyroidectomy hypocalcaemia: a multi-centre experience.

PURPOSE: Hypoparathyroidism is one of the most common and most feared complications of total thyroidectomy (TT). The aim of this study is to detect possible markers that may facilitate early tracing of hypocalcaemia-prone patients in order to reduce clinical cost by optimizing patient discharge and to avoid unnecessary treatment. METHODS: Over an 18-month period, 995 patients, 23 % male and 77 % female, aged 52.9 ± 13.4 years, underwent TT in ten Lombardy hospitals. The following parameters were analyzed: calcaemia before and 12-24 and 48 h after surgery, pre- and post-operative parathyroid hormone (PTH) at 24 h and pre-operative 25OH vitamin D. RESULTS: Mortality was nil and morbidity was 22.4 %. Mean 24-h calcaemia and PTH were 2.17 ± 0.15 mmol/l and 31.81 ± 20.35 pg/ml, respectively; mean 24-h PTH decay was 36.7 ± 34.12 %. Four hundred seventy-three (47.5 %) patients were hypocalcaemic at discharge; 142 of whom had transient hypoparathyroidism that became permanent in 27. Patients developing hypocalcaemia had significantly higher values of PTH and calcium decay. At multiple logistic regression, only 24-h calcium decay, PTH drop and the presence of symptoms and parathyroid auto-grafting were significantly related to hypoparathyroidism. The association of these factors had a 99.2 % negative predictive value (NPV) for the development of hypoparathyroidism. A 70 % PTH drop had a 93.75 NPV for transient hypoparathyroidism. A 12 % calcaemia decay had a 95.7 NPV for hypoparathyroidism. CONCLUSIONS: Hypocalcaemic asymptomatic patients with less than 70 % PTH and 12 % calcaemia decay may be safely discharged without treatment. Symptomatic patients and those with parathyroid grafting should receive calcium and vitamin D.

Management of papillary microcarcinoma of the thyroid gland.

DESIGN: To investigate the frequency, treatment and clinical behaviour of differentiated microcarcinoma of the thyroid gland (PTMC). PATIENTS AND METHODS: Out of 376 patients submitted to surgical treatment for differentiated thyroid cancer from June 1980 to October 2003, 77 had been identified has having a PTMC (63 females, 14 males; mean age 43+/-13 years). Sixty-seven patients (87%) met the AMES risk definition for low (group I) and 10 (13%) for high-risk (group II) definition. The surgical procedures were lobo-isthmusectomy (n=14) or subtotal thyroidectomy (n=20) and total thyroidectomy (n=43) with node dissection in 15 cases. Follow-up ranging from 9 to 274 months (mean 124+/-84). RESULTS: Overall patient survival rates were 100 and 94% at 20 years in groups I and II, respectively (p=ns). There were no significant differences in surgical complications and in survival in patients submitted to total thyroidectomy when compared to partial thyroid resection. The presence of cervical node metastasis did not affect patient survival (p=0.8). The overall mean survival time was 266 months. CONCLUSIONS: Despite the overall excellent prognosis, PTMC was associated with a 1% disease-related mortality, a 2.5% local recurrence rate, 1% lymph-node recurrence rate, and 1% distant metastasis rate. We recommend total thyroidectomy accompanied by modified neck dissection if enlarged nodes are diagnosed.

Modified neck dissection in the treatment of differentiated thyroid carcinoma.

The prognosis of differentiated carcinoma of the thyroid has been reported to be extremely favourable. Previous studies have concluded that lymph node metastasis do not affect survival rates in patients with differentiated thyroid carcinoma. Therefore, nodal metastasis has not been evaluated as a prognostic factor in recent definitions of risk groups. To determine the significance of nodal disease, we reviewed 219 consecutive patients with differentiated thyroid cancer (191 papillary, 14 follicular and 14 Hurtle cell carcinomas). Fifty-five patients were treated with modified neck dissection and all of them received adjuvant radioiodine. There were recurrences in 25 patients (11.4%), with follow-up ranging from 6 months to 14 years. Systemic disease occurred synchronously in two patients, and four patients died of thyroid carcinoma.

Repeated hepatectomy for colorectal metastasis.

Between January 1981 and December 1995, 12 patients, who previously underwent hepatic resection for colorectal metastases, were selected for a second liver resection for isolated liver recurrence. Mean interval between first and second resection was 16 months. Eight patients had solitary and 4 multiple metastasis. Two major hepatectomies and 11 wedge resections were performed. Mean follow-up was 37 months. No mortality and 33% morbidity was observed. Three and 5-year actuarial survival rates were 71% and 42%, while disease-free survival was 30%. No patient, primary tumour, or metastases' characteristics were significantly associated to survival. Surgical resection is the only therapy that could offer reasonable chance of long term survival and, in selected case, of cure. A careful patients' selection as well as an accurate surgical technique are essential to reduce post operative mortality and morbidity.

Total thyroidectomy in the treatment of thyroid cancer.

Considerable controversy exists about the most appropriate treatment for thyroid cancer. In this report the authors present their experience of 189 patients, all of whom had a total thyroidectomy between June 1980 and December 1993. The age of the patients ranged from 11 to 78 years (mean age: 42 years), there were 144 women and 45 men. Histological types were: 146 papillary, 16 medullary, 10 follicular, eight Hurtle, six insular and three undifferentiated. Coexistent lesions included: 22 thyroiditis, 17 adenomas, one Graves' disease and 22 benign goitre. Fifty-six (29.6%) patients had multifocal papillary cancer (bilateral in 45 cases). Surgical complications included 20 cases of transient recurrent laryngeal nerve palsy, 16 cases of transient and one of permanent hypoparathyroidism, and one respiratory obstruction due to bilateral recurrent laryngeal nerve palsy that required temporary tracheostomy. Two patients were reoperated on due to bleeding. Ninety per cent of patients were discharged within 3 days of thyroidectomy. One hundred and fifty patients were evaluated for 131I treatment by a standardized dosimetry procedure 4 weeks after surgery. Dosimetry was also used to calculate therapeutic 131I doses. Seventy-six patients did not show a 131I uptake above background levels, 56 underwent therapeutic 131I, while in the 18 patients who showed an abnormal uptake of 131I it was decided not to give the therapeutic dose. The authors conclude that total thyroidectomy can be performed with a minimum of permanent disability in patients with malignant thyroid tumours. The theoretical and practical advantages of this kind of surgical strategy make it the treatment of choice for thyroid cancer.

Avidin-biotin system in radioimmunoguided surgery for colorectal cancer. Advantages and limits.

PURPOSE: Radiolabeled monoclonal antibodies (MAbs) have been reported to allow tumor intraoperative detection by means of a gamma-detecting probe. The technology is called the Radioimmunoguided Surgery (RIGS) system. The main inconveniences of the method are 1) the long interval needed for clearance of unattached MAbs from the patient's body, between the injection of the MAb and surgery, and 2) the low sensitivity of current MAbs used in detecting small tumors. We describe a new method to overcome these inconveniences using biotinylated MAbs and avidin in order to obtain a rapid blood clearance of the radiolabeled MAbs both anticarcinoembryonic antigen and antitumor-associated glycoprotein-72 MAbs. METHODS: Twenty patients with primary and recurrent colorectal cancer have been enrolled in the study; 125I-biotinylated MAbs FO23C5 (anticarcinoembryonic antigen) and B72.3 (antitumor-associated glycoprotein-72) followed by cold avidin were injected in 13 patients and 7 patients, respectively. RESULTS: A decrease of 94 +/- 3 percent of circulating radioactivity was achieved in 3 to 5 days. Patients underwent surgery approximately seven days after MAb injections rather than after four weeks. Tumors were localized in 14/20 (70 percent) patients (true positive), 2 (10 percent) were false negative, and 4 (20 percent) were true negative. The overall sensitivity level in early-stage primary cancers was 37 percent when related to the presence of disease and 75 percent when related to antigenic expression. The sensitivity for more advanced cancer and for recurrences was 100 percent. Moreover, the in vivo tumor targeting of biotinylated MAb was demonstrated in frozen tumor section by direct streptoavidin-peroxidase staining. CONCLUSIONS: The avidin-biotin system may enhance applicability and effectiveness of radioimmunoguided surgery (RIGS).

Tetanus antibodies at booking in a Nigerian obstetric population.

Eighty-four consenting ante-natal patients at the University of Nigeria Teaching Hospital, Enugu, were examined for tetanus antibodies at booking. Only 28.6% had detectable serum antibodies. Although 73.8% were immunized within three years prior to investigation, only 37.1% had measurable antibodies. It was found that the longer the interval from previous immunization, the fewer the number with detectable antibodies and the lower the titres. Possible explanations for these findings are discussed and recommendations made.

PIP: Vaccinating pregnant women against tetanus can passively protect offspring against the disease. The earlier in the pregnancy this occurs, the greater the chances of neonate protection. In some countries pregnant women do not seek health support until well into their pregnancy, which may not allow sufficient time for a tetanus vaccine to provide full protection. Reported here are findings on 84 pregnant Nigerian women at the time of their initial medical appointment. Blood was analyzed for tetanus antibodies using the hemagglutination method. 24 women (28.6%) had measurable antibody to tetanus. 62 women (73.8%) had received a tetanus vaccine within the last 3 years. The data suggest that the longer the time interval since previous immunization, the smaller the number of patients with detectable antibodies; generally, titer levels became lower as time passed. A complete immunization series is needed for each pregnancy and is strongly recommended. A more intensive health education program is also needed and should stress the importance of early prenatal care and the tetanus immunization program.

Medullary-thyroid carcinoma - clinical-evaluation of 19 cases.

Medullary thyroid carcinoma (MTC) accounts for 5-10% of thyroid malignancies and occurs either as a sporadic or as a familial form. The familial form is inherited in an autosomal dominant pattern, and it is clinically expressed as multiple endocrine neoplasia (MEN), types IIa and IIb or as familial MTC alone. It is possible to make an early diagnosis in patients who have the familial form of the disease as well as to perform an organ specific localisation regarding possible spread of the disease. Calcitonin is a major product of MTC cells and represent the most used tumour marker for diagnosis and evaluation of prognosis. The purpose of this investigation is to analyse our experience with patients treated for MTC in the period 1980-1993.

The response to varied timing and spacing of tetanus toxoid administration in pregnancy.

One hundred and sixty-eight pregnant women at the University of Nigeria Teaching Hospital, Enugu, Nigeria, were studied for their response to varied timing and spacing of tetanus toxoid administration. In patients who started immunization before the third trimester of pregnancy, the longer the interval between the two doses, the better the response. In contrast, when immunization was started in the third trimester, the longer the interval between the two injections, the poorer the response. In all cases, the presence of antitetanus antibodies at booking conferred better response. In addition, the titres of antibodies in all patients who responded continued to rise till delivery. The significance of these findings is discussed and recommendations made.

Incidental tuberculous endometritis in premenstrual curettings from infertile women in eastern Nigeria.

A total of 4700 specimens of premenstrual endometrial curettings from infertile women were reviewed at the University of Nigeria Teaching Hospital, Enugu. Ten cases of tuberculous endometritis were found, giving a prevalence of 0.2%. The significance of this low prevalence is discussed. It is suggested that more deliberate efforts should be made to search for genital tuberculosis in infertile women in developing countries.

Antenatal screening for syphilis at the University of Nigeria Teaching Hospital, Enugu, Nigeria--a six year survey.

Between January 1979 and December 1984, 29,083 out of 42,515 antenatal patients booking at the Antenatal Clinic of the Department of Obstetrics and Gynaecology of the University of Nigeria Teaching Hospital, Enugu, underwent full screening for syphilis. The results showed that 890 patients (3.06%) had positive VDRL test. Of those that reacted positively in the VDRL test, 103 (11.6%) had positive TPHA test. A prevalence rate of sero-positivity of 0.35% was obtained indicating a low incidence of syphilis in our pregnant women compared with results from other parts of Nigeria. A strong recommendation was made to treat all seropositive cases whether there was historical or clinical confirmation of syphilis or not.

Incidence of yeasts in pregnant and non-pregnant women in Nigeria.

The yeast flora of vagina and associated sites (cervix, urethra, perineum and rectum) in 224 pregnant and 106 non-pregnant Nigerian women was investigated. A variety of yeasts represented by 12 species were isolated. Candida albicans was the most frequently isolated species in both groups, accounting for 63.6% of the isolates from pregnant women and 44.8% of the isolates from non-pregnant women. Other species of yeasts infrequently or occasionally encountered were Torulopsis glabrata, C. tropicalis, C. pseudotropicalis, C. parapsilosis, C. krusei, C. guilliermondii, C. stellatoidea, T. candida, T. etchellsii, Saccharomyces cerevisiae, Rhodotorula rubra and Cryptococcus uniguttulatus. C. albicans was also the principal species recovered from symptomatic cases in both groups, followed by T. glabrata in pregnant women and C. parapsilosis in non-pregnant women.

Pelvic abscess in gynecologic patients.

A survey of an 8-year period in which 37 cases of pelvic abscess occurred in a Nigerian hospital department of obstetrics and gynecology is presented. All 37 women were surgically treated; one death occurred postoperatively. A regimen of 400 mg of metronidazole three times daily combined with appropriate antibiotics is recommended as the treatment of choice, even where laboratory confirmation of anaerobic involvement is unavailable.

Perforation of the appendix during pregnancy: a rare complication of endometriosis. Case report.

Perforation of the appendix in a 23-year-old Nigerian Igbo woman during the 35th week of pregnancy is reported. In the perforated area, the wall of the appendix was replaced largely by decidualized endometriotic tissue.