The interplay between vitamin D and COVID-19: protective or bystander?

The world is currently facing the COVID-19 pandemic, caused by the novel Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). Due to a lack of specific treatment and prophylaxis, protective health measures that can reduce infection severity and COVID-19 mortality are urgently required. Clinical and epidemiological studies have shown that vitamin D deficiency can be linked to an increased risk of viral infection, including COVID-19. Therefore, in this review, we looked at various possible roles of vitamin D in reducing the risk of COVID-19 infection and severity. We describe in this article that individuals at high risk of vitamin D deficiency should consider taking vitamin D supplements to keep optimal concentrations. Moreover, we discuss different possible mechanisms by which vitamin D can efficiently reduce the risk of infections through modulation of innate and adaptive immunity against various types of infections. It is advisable to perform further studies addressing the observed influence of vitamin D levels to reduce the risk of COVID-19 infection and mortality.

Postmastectomy radiotherapy reduces locoregional recurrence in elderly women with high-risk breast cancer.

AIMS: Clinical trials of adjuvant radiotherapy after mastectomy have largely excluded women aged 70 years or over, even though they comprise 30% of the breast cancer population. This study examined outcomes in elderly women with high-risk breast cancer treated with or without postmastectomy radiotherapy (PMRT). MATERIALS AND METHODS: Data were analysed for 233 women aged 70 years or over with high-risk breast cancer (tumours > 5 cm or > or = 4 positive axillary nodes) treated with mastectomy and referred to the British Columbia Cancer Agency from 1989 to 1997. Tumour and treatment characteristics were compared between two cohorts: women treated with PMRT (n = 147) vs women treated without PMRT (n = 86). Univariate and multivariate analyses of 10-year Kaplan-Meier locoregional recurrence (LRR), distant recurrence, breast cancer-specific survival and overall survival were carried out. RESULTS: Median follow-up time was 5.5 years. The distribution of tumour sizes was similar in the two groups. Compared with women treated without PMRT, higher proportions of women who underwent PMRT had four or more positive nodes (83% vs 67%, P = 0.01) and positive surgical margins (14% vs 4%, P = 0.02). Systemic therapy, used in 94% of women, was comparable in the two cohorts (P = 0.63). Elderly women treated with PMRT had significantly lower LRR compared with women treated without PMRT (16% vs 28%, P = 0.03). No differences in distant recurrence, breast cancer-specific survival or overall survival were observed in the two treatment groups (all P > 0.05). On multivariate analysis, the omission of PMRT and the presence of high-grade histology were significant predictors of LRR, whereas an increasing number of positive nodes was significantly associated with distant recurrence and overall survival. CONCLUSIONS: In women aged 70 years or over with tumours greater than 5 cm or four or more positive nodes, significantly lower LRR was observed in women treated with radiotherapy compared with women treated without radiotherapy. PMRT should be considered in the management of elderly women with these high-risk characteristics.

Tubular carcinoma of the breast: a population-based study of nodal metastases at presentation and of patterns of relapse.

Tubular carcinoma of the breast (TCB) is a recognized histologic variant of infiltrating ductal carcinoma (IDC) and has been considered to have a comparatively favorable prognosis. However, previous studies have been based on small numbers of cases, some pure TCB and some mixed histology, or have not employed an appropriate comparison group. In this study 171 pure TCB cases and a comparison group of 386 cases with grade I (well differentiated) IDC were identified in a population-based database maintained by the British Columbia Cancer Agency (BCCA). The proportion of cases with axillary nodal involvement at presentation was lower in TCB cases than in the grade I IDC comparison group (12.9% and 23.9%, respectively; p < 0.05). Low-risk tumors (T1 and without vascular lymphatic or perineural invasion) were more prevalent in the TCB patients than in the grade I IDC patients (66.7% and 60.0%; p < 0.05). Low-risk TCB cases had a significantly lower rate of nodal metastases at presentation than low-risk grade I IDC cases (7.0% and 13.2%; p < 0.05). Kaplan-Meier and log-rank analyses indicated a statistically significantly lower rate of local recurrence in TCB cases than among IDC cases (p < 0.05) and a trend toward a lower rate of systemic relapse in TCB cases (p = 0.07). However, no difference in disease-specific survival was observed between TCB cases and grade I IDC comparisons. We conclude that the biologic behavior of TCB was more favorable than that of a comparison group of IDC cases. In view of the low incidence of axillary node metastases at presentation in the low-risk TCB subset (7%), axillary dissection may be omitted as part of the initial surgical management in these patients.

Colonic inflammation found at diagnosis of juvenile retention polyps in pediatric patients.

OBJECTIVE: The finding of colonic inflammation concurrently with a juvenile retention polyp (JRP) may have prognostic value. However, the significance of abnormal mucosal histology with JRP has not been evaluated. We evaluated the significance of mucosal histology at the time of JRP removal with respect to future development of inflammatory bowel disease (IBD) and polyp recurrence. METHODS: The medical records of patients who had an endoscopic polypectomy performed at the Children's Hospital of Philadelphia (CHOP) from 1/1/87 through 4/30/98 were retrospectively reviewed. RESULTS: JRP was histologically identified in 96 patients. A total of 54 patients had colonic mucosal biopsies: 30 (55.6%) had normal histology and 24 (44.4%) had colitis. Of the 24 patients with colitis, 14 patients (58.3%) had inflammation at the polyp site. Twelve of these patients had additional inflammation elsewhere in the colon. Nine (37.5%) had inflammation elsewhere in the colon; however, biopsies around the polyp site were not obtained. One patient with inflammation did not have the location of the polyp documented. Four patients (16.7%) had IBD at the time of polypectomy; two were diagnosed prior and two coincident with JRP. None have subsequently been diagnosed with IBD. There was no difference in polyp recurrence between those with or without inflammation (16.7% [4/24] vs 10.0% [3/30]). The mean follow-up period was 72.4 months (range, 5-142 months). CONCLUSIONS: In our experience, histological mucosal inflammation is a common finding with JRP. This inflammation may be a precursor for the development of JRP but has no predictive value for polyp recurrence. This colitis does not seem to be associated with IBD.

Normal thiopurine methyltransferase levels do not eliminate 6-mercaptopurine or azathioprine toxicity in children with inflammatory bowel disease.

6-mercaptopurine (6-MP) and azathioprine (AZA) are used to treat inflammatory bowel disease (IBD). Side effects include infection, leukopenia, hepatitis, and pancreatitis. The level of thiopurine methyltransferase (TPMT), which metabolizes 6-MP to 6-methylmercaptopurine, may reflect the risk of side effects. We sought to evaluate the relationship between the side effects of these medications and the TPMT level of pediatric patients with IBD. The medical records of our patients who were diagnosed with IBD and who received 6-MP or AZA were reviewed for measured TPMT levels. All red blood cell (RBC) TPMT levels were determined at the Mayo Medical Laboratories, Rochester, MN. The occurrence of leukopenia, elevated aminotransferases, and pancreatitis was evaluated. Twenty-two patients, mean age 13.7 years, received 6-MP or AZA and had TPMT levels measured. The TPMT levels ranged 10.7-27.5 U/mL RBC with a mean of 17.2 +/- 3.2 U/mL RBC. Two children had levels below the accepted norm of 13.8 U/mL RBC. One of these patients (50%) developed both elevation of aminotransferases and leukopenia. Of all, 20 children had normal levels, 3 (15.0%) exhibited side effects: hepatitis (n = 2) and leukopenia (n = 1). We conclude that side effects of 6-MP or AZA occur despite normal TPMT levels.

Experiences with 6-mercaptopurine and azathioprine therapy in pediatric patients with severe ulcerative colitis.

BACKGROUND: The effectiveness of 6-mercaptopurine combined with azathioprine in treating severe ulcerative colitis has been shown in several adult studies. Reported pediatric experiences are rare. The purpose of this study was to investigate the safety and the potential efficacy of 6-mercaptopurine and azathioprine in the treatment of active ulcerative colitis in a pediatric population. METHODS: The medical records of patients with active ulcerative colitis who were under observation at The Children's Hospital of Philadelphia and its satellite clinics from January 1984 through December 1997 were retrospectively reviewed. Patients were included who had received a diagnosis of ulcerative colitis, who met no criteria for Crohn's colitis, and who had received treatment with 6-mercaptopurine and azathioprine. They were then analyzed for the development of side effects, the indication to use 6-mercaptopurine and azathioprine, and the ability to discontinue corticosteroid use in those patients taking 5-acetylsalicylic acid products who were corticosteroid-dependent or whose disease was refractory to treatment. Excluded from the corticosteroid analyses were patients who underwent surgery for their disease and patients treated with 5-acetylsalicylic acid only. Statistical analysis was performed by the Kaplan-Meier survival curve and paired Student's t-test. RESULTS: In a review of 200 medical records of patients with active ulcerative colitis, 20 patients met the criteria. The patients' average age at the initiation of treatment with 6-mercaptopurine and azathioprine was 13.8 years. Sixteen patients (80%) were corticosteroid dependent and 3 (15%) had ulcerative colitis refractory to corticosteroid treatment. One patient had severe colitis treated with 5-acetylsalicylic acid only. Discontinuation of corticosteroid was accomplished in 12 (75%) of 16 patients. The median time to discontinuation of corticosteroid after initiation of 6-mercaptopurine and azathioprine therapy was 8.4 months. Eight patients (67%), observed from 3 months to 65 months, have continued without corticosteroid therapy. Side effects included pancreatitis and shingles that resulted in discontinuation of 5-acetylsalicylic acid, leukopenia corrected by withholding 6-mercaptopurine, and self-resolved hepatitis. CONCLUSIONS: The data support the safety of 6-mercaptopurine and azathioprine use in the treatment of pediatric patients with ulcerative colitis; side effects were minimal and reversible. Eighteen (90%) of 20 patients tolerated the therapy well. The results also show that 12 (75%) of 16 pediatric patients with ulcerative colitis will benefit from the use of 6-mercaptopurine and azathioprine after initial discontinuation of corticosteroid therapy. Although 6-mercaptopurine and azathioprine may not prevent further relapses, medical management of these flares may be less intense and may not require long-term corticosteroid use. Prospective clinical trials in pediatric patients are necessary to delineate further the role of 6-mercaptopurine and azathioprine in pediatric ulcerative colitis.

Single toxin detection is inadequate to diagnose Clostridium difficile diarrhea in pediatric patients.

BACKGROUND & AIMS: Clostridium difficile is an important cause of symptomatic diarrhea in pediatric patients. The bacterium produces two toxins, although many laboratories assay for only one. We questioned this diagnostic approach when patients had positive results for C. difficile at our institution, but initially had tested negative at outside laboratories. METHODS: We retrospectively analyzed relative frequencies of C. difficile toxin A alone, toxin B alone, and toxins A and B from pediatric patients with diarrhea. Results were stratified according to toxin detection and patient age. RESULTS: Of 1061 specimens, 276 (26.8%) were positive for C. difficile toxin(s). Fifty-one (18.5%) were positive for toxin A alone, 133 (48.2%) for toxin B alone, and 92 (33.3%) for both toxins. Assaying for toxin B identified C. difficile infection more frequently than did assaying for toxin A (P < 0.0001). The frequency of toxin B detection was significantly higher for older children but not for infants. CONCLUSIONS: Testing for C. difficile toxin A or toxin B alone will result in more frequent misdiagnosis than testing for both toxins. This practice may lead to inappropriate further invasive investigations in children, although this finding may not be applicable to adults.

Introduction of 6-mercaptopurine in Crohn's disease patients during the perioperative period: a preliminary evaluation of recurrence of disease.

BACKGROUND: Recurrence of Crohn's disease after surgery is a common occurrence, pointing to the need for a strategy to prevent recurrent disease. We report the postoperative course of 10 patients who required intestinal resections for complications related to Crohn's disease. METHODS: All patients had a Pediatric Crohn's Disease Activity Index score of 10 or greater. Among these patients, 5 began treatment with 6-mercaptopurine in the perioperative period. All 10 had received various combinations of prednisone and salicylate compounds. Patients who were given 6-mercaptopurine did not discontinue the medication until 2 years after the surgery. RESULTS: To date, none of the five patients who were placed on 6-mercaptopurine have had recurrence of their Crohn's disease (mean disease-free period 32.6 +/- 18.4 months). Among those five patients not receiving 6-mercaptopurine there have been three relapses (mean time to relapse 3.7 +/- 1.2 months). Log-rank sum analyses of Kaplan-Meier survival curves show benefit to patients receiving 6-mercaptopurine in preventing relapses after intestinal resection (p < 0.05). CONCLUSIONS: Although the underlying pathophysiologic reasons leading to the high relapse rate after intestinal surgery in Crohn's disease are unknown, we conclude that treatment with 6-mercaptopurine in the perioperative period may be warranted to help prevent the recurrence of Crohn's disease after surgery.

Pulmonary complications of bone marrow transplantation: the impact of variations in total body irradiation parameters.

In this article we report and discuss the pulmonary complications in patients who received a single exposure total body irradiation (TBI) to a total dose of 7.5 Gy at a dose rate of 0.15 Gy/min, a TBI regimen which has the advantage of being given in a single, relatively short exposure, with an active treatment time of less than 1 hour. This forms a part of the bone marrow transplantation programme for the management of certain haematological malignancies at the Leicester Regional Centre. Between July 1986 and October 1990, we treated 31 patients with such a regimen. Full respiratory function tests (RFT) were carried out, prior to TBI, in the majority of patients. After a mean follow-up period of 34 months, 13 patients were alive; full RFT were repeated in all of them. Of the total of 31 patients, only one patient died, from late non-specific pneumonitis; in this case, high dose busulphan was added to conventional cyclophosphamide and TBI. Another patient died as a direct result of cytomegalovirus pneumonia. Comparison of pre- and post-TBI RFT showed no resultant obstructive, restrictive or transfer factor defects. In the three patients who did not have pre-TBI RFT, post-TBI RFT did not reveal any significant change from expected values for age, sex and height. Several major centres have reported their experience using various combinations of different total doses, dose rates and fractionations. Having compared our results with theirs, we conclude that, following this relatively short and convenient single exposure TBI, there is no evidence of increased acute or chronic pulmonary toxicity.

Follicle stimulating hormone levels as a predictor of recovery of spermatogenesis following cancer therapy.

Infertility, both temporary and permanent, is a well-recognized complication of certain cancer treatments. The main objective of this study was to determine whether recovery of fertility in male patients, could be predicted by monitoring changes in serum follicle stimulating hormone (FSH) levels. Twenty male patients participated in the study. Sperm counts and serum FSH levels were measured before, during and after treatment. Azoospermia was universal in all 20 patients during the first year, with significantly raised FSH in almost all the patients. Reduction of FSH levels during the second year was frequently followed by recovery of spermatogenesis. Patients in whom the FSH did not fall during the second year were highly unlikely to regain fertility.

Bilateral pneumothorax secondary to metastatic angiosarcoma of the breast.

Bilateral spontaneous pneumothorax is a rare complication of pulmonary metastases. We report a 44 year old woman who developed this complication a few months after undergoing mastectomy and postoperative radiotherapy for primary angiosarcoma of the breast.

Changes in human milk vitamin E and total lipids during the first twelve days of lactation.

Our previous study showed vitamin E deficiency in newborns (69.7%) and mothers at term (85.9%) when the ratio between serum vitamin E in mg/dl and total lipids in g/dl was used as an indicator of vitamin E status. This study was conducted to determine the human milk content of vitamin E. During the first 12 days of lactation milk vitamin E levels remained almost constant (day 1, 0.68 mg/dl; day 12, 0.65 mg/dl), milk total lipid levels increased daily (day 1, 1.11 g/dl; day 12, 3.60 g/dl), and the ratio between milk vitamin E and total lipids dropped steadily (day 1, 1.3; day 12, 0.2). In spite of this drop in vitamin E status, it is unlikely that vitamin E availability will be affected in neonates, because normal neonates absorb milk fats well and this ability increases with age.

Early breast-feeding patterns in a Malaysian maternity hospital, 1980-1983.

PIP: The promotion of commercial infant formulas in hospitals making such formulas freely available to new mothers has been prohibited by a set of rules 1st enforced in Malaysia in 1981. This report studies the influence this development has had on infant feeding patterns among health mothers over 3 different time periods: the period before this code of ethics was enforced in 1980-1981 (29,401 cases); the period immediately after from June to December of 1982 (7,833 cases); and the last phase from January to April of 1983 (4,380 cases). Over the 3 phases of the study, choice of breastfeeding increased consecutively from 4.1% to 10.5% and finally 31.7%. Formula feeding increased also, from 1.5% to 2.0% and 2.4%. While mixed feeding was the most popular choice, its incidence declined from 94.4% in 1981 to 65.9% in 1983. Differences among ethnic groups were not statistically significant in the early studies, while in 1983 the incidence of breastfeeding among Chinese, Indians and Malays was 33.1%, 32.1% and 31.0%, respectively. For maternal age groups studied, the increase in breastfeeding was greater for the at-risk groups (mothers less than 20 years and over 35 years of age). This same trend was seen among parity groups, with at-risk groups being parity 1 and parity 5. When socioeconomic status was compared, all classes showed an increase in breastfeeding, but the largest increase was among the highest socioeconomic class. Although mixed feeding is still favored, there is a definitive trend toward breastfeeding, perhaps partly helped by the introduction of the code of ethics against free formula distribution in hospitals.^ieng

The National Family Planning Program: its impact on perinatal mortality.

PIP: The aim of this investigation is to study the effect of family planning on declining maternal and infant mortality rates in Malaysia since the National Family Planning Program began operation in May, 1967. Data were derived from the registration of vital events and reports from the Malaysian Family Life Survey conducted in 1978, and demonstrate declines in maternal and infant mortality rates. Although this is a result of a combination of factors (e.g., socioeconomic development, high quality health and medical services) the contribution of family planning is significant. Between 1957 and 1980 the maternal mortality rate declined by 80%. High risk births declined from 10.2% to 8.2% for mothers under age 20, and from 15% to 13.7% for mothers over age 35 during the 1967-1977 decade. From 1955 - 1980 the infant mortality rate declined by 68.2% to a level of 24.9/1000 live births; this may be partly due to the shift to lower order births (and therefore low risk) as a result of better family planning. Perinatal mortality declined 6.7% in the pre-implementation years (1957 - 1967) and 19.8% in the post-implementation years (1967 - 1977). Low birthweight is a significant correlate of infant survival, and data from this study indicate that birthweights increase with maternal age up to 30-34 years, then begin to decrease. Birthweights are also lower (and infant mortality higher) for babies born at birth intervals of less than 15 months. Therefore, concerted efforts in family planning education need to be directed to vulnerable groups such as young mothers (under 19) and older mothers (over 40).^ieng

Pertinent considerations in preterm infant management.

Urgent demands made on the ill-equipped developing organ-systems of the preterm newborn to adapt to an extrauterine independent existence lead to the specific clinical problems seen. The degree and severity of these adaptive adjustment changes may be influenced by obstetric and environmental factors which could either precipitate or aggravate some of these problems. The management of the preterm newborn soon after delivery can thus be competently achieved by an anticipatory team approach involving the obstetrician, pediatrician (neonatologist) and nursing personnel. A predelivery decision-making process would involve the issue of when and how to deliver, the assessment of pulmonary maturity and use of steroids to accelerate pulmonary maturation. Immediate management at birth centers on cardio-pulmonary resuscitstion and prophylaxis against cooling. Following this, respiratory, hematalogic, renal cardiovascular, gastrointestinal and metabolic adaptative disorders must be anticipitated and overcome. Continuing care demands continuous electronic monitoring of vital signs, clinical monitoring and vigilance to provide adequate fluids and nutrients along with a consideration to allow considerate patient-infant bonding. Aversion of measures which are believed to contribute to sequelae such as bronchopulmonary dysplasia, retrolental fibroplasia and neurologic and intellectual impairment are also crucial issues. Follow-up is thus mandatory. The costs of all these in skilled manpower and economic terms are expectedly high. These challenges have proven to be exciting and the results rewarding.